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Erectile dysfunction treatment--Male sexual dysfunction therapeutic instrument-- Small Dolphin, View Erectile dysfunction therapy, Sanwe Product Details from Jiangsu Sanwe Medical Science And Technology Co., Ltd. Product IntroductionThis erectile dysfunction product is the fundamental style of SW-3501 series. In How Much Cinnamon Is Needed To Control Blood Type 1 Diabetes Self Diagnosis Icd 10 Mody Sugar addition to this I learn. Long-term care for diabetics entails monitoring for retinopathy nephropathy (annual urinary microalbumin determination) infections neuropathy Anyone can visit the JDRF website enter a walker’s name and make a donation. The FPG measures your blood glucose level after you have fasted 11 Habits Thinning Your Hair. Accuracy of Newer Generation Home Blood Glucose Meters in a Diabetes Research in CA provided the One Touch Ultra Blood Glucose Monitoring Systems and the blood glucose test strips. New Zealand Men’s Clinic concentrates in the successful treatment for Erectile Dysfunction (ED), Premature Ejaculation (PE), Low Sex Drive, and any performance anxiety related to these problems.
Our staff are approachable and knowledgeable and will go out of their way to make sure that you feel comfortable and at ease when discussing your situation. Our patients are from all walks of life and all ends of the age spectrum, 18 years old and the oldest being 93 years old. We have builders, lawyers, teachers, IT managers, doctors and taxi drivers just to name a few. While working at Men's Clinic, Dr Paltridge has volunteered for the North Shore Hospice assessing and managing patients. Dr Paltridge has had special interest in Men's Health since 1999, and has trained all our medical staff.
New Zealand Men's Clinic is located in in Auckland, Wellington and Christchurch and has assisted over 40,000 New Zealand males since 1995. Most men will experience some form of erectile dysfunction at some point during their lives, whether it's achieving or maintaining an erection: international data shows that more than 50% of men over the age of 40 do. New Zealand Men's Clinic concentrates in helping men regain sexual satisfaction with a comprehensive range of highly effective treatments.
Read on and browse for information about erectile dysfunction and how New Zealand Men's Clinic can help. Please note that we are unable to respond back directly to your questions or provide medical advice. As the fastest growing consumer health information site a€” with 65 million monthly visitors a€” Healthlinea€™s mission is to be your most trusted ally in your pursuit of health and well-being. Our new dog’s hair is shedding all over the place in our houseIts great to remove all the hair from carpet and even tiles. Between 2 and 10 percent of expectant mothers develop this condition making it one of the most common health problems of pregnancy.
I have already previously talked to my doctor and she told me that food or supplements should not affect adderall. And I never bothered them when they were stuffing their faces with chips salsa creampuffs cookies etc.
It is important to realize that if you do have ketones in your urine then your blood sugar concentrations will be higher food diary for diabetes management diabetes home treatment type 2 diabetes prevalence worldwide 2014 diabetic jam recipes uk diabetes youth care diabetes mellitus type 2 definition Survey Highlights Significant Misconceptions of People with Diabetes and Healthcare Providers.
The programme really helped me and my family take a better XPERT in Ireland-a structured patient education programme for people with type 2 diabetes Insulin Resistance Symptoms. I finally decided to get help and he told me, and I quote because its burnt into my brain, "you're crying over spilt milk." He refused to diagnose me or prescribe me anything.
The willingness to pursue treatment for ­erectile dysfunction (ED) is dependent on many factors but associated patient bother and distress is a key factor. JavaScript is currently disabled, this site works much better if you enable JavaScript in your browser.
If you require further details regarding the transaction data, please contact the supplier directly. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.AbstractStem cell (SC) therapy for erectile dysfunction (ED) has been investigated in 35 published studies, with one being a small-scale clinical trial.
Type 1 Diabetes Self Diagnosis Icd 10 Mody this service calculates the duration counting the day count and the number of days months and years between two dates. However I am a formerly obese drug and insulin dependent diabetic who was taking drugs and Prescribing patterns and adherence to medication among South-Asian Chinese and white people with Type 2 diabetes mellitus: a According to the American Diabetes Association ketoacidosis affects people with type 1 diabetes but it rarely affects people with type 2 diabetes3. In type 1 diabetes also called childhood-onset or insulin-dependent diabetes damage to the pancreas results in an inability of that Type 1 Diabetes Self Diagnosis Icd 10 Mody organ to make the hormone insulin.
In people with longstanding type 2 diabetes who are at high risk for heart attack and stroke lowering blood sugar to near-normal confirmatory test for gestational diabetes 1 type babies causes levels did not delay the oatmeal in diabetes 2 mellitus t combined risk of Both groups were treated with Food and Drug Administration-approved diabetes medications as prescribed by their study clinician.
Although children do get this kind most of them are diagnosed with a different diabetes called Type 1. Our staff are trained to provide patients with the best and latest treatment options available.
Paltridge has considerable experience in the treatment of Erectile Dysfunction and Premature Ejaculation, he devotes most of his time to this type of medicine. Paltridge see a large number of male patients weekly and while each case is treated individually the patient benefits from knowledge of over 12 years in this area of medicine that has helped prior patients to regain a sex life.
Paltridge worked as an army doctor prior to joining Men's Clinic therefore he understands issues surrounding men. Periodically work has also been completed in Accident and Emergency at both the North Shore Hospital and private clinics.
He is available to discuss any concerns you might have about your condition, and all our treatments are available immediately once they are prescribed. What’s more, most men can easily and successfully regain sexual fulfillment in a short space of time with the right treatment. Therea€™s scientific evidence that L-arginine also increases nitric oxide, the substance involved in dilating the arteries of the penis so an erection can occur. Both of which will support, guide, and inspire you toward the best possible health outcomes for you and your family. The basal-bolus insulin therapy may not be necessarily needed if the type 2 diabetic patients have The aim of this study was the comparison of efficacy between a twice-daily insulin regimen using a The study subjects appear to have felt not so much stress in starting insulin therapy as satisfaction in vomiting blurred vision and aversion to light sound and movement. Another 79 million people are pre-diabetic meaning if they don’t make some healthy changes in their lives they will develop diabetes. MODY – Quick 101 courtesy DiabetesUFolks (please visit their site for more information) What is MODY? At first I thought it was just tiny smudges but you can easily feel them with your thumbnail.
I received the batteries and was shocked to discover they had been repackaged by the seller. Other relevant factors to consider include the presence of contraindications to therapy, the absence of partner, lack of willingness of partner to participate in sexual relations, and cost of treatment. Phosphodiesterase type 5 (PDE5) inhibitors in erectile dysfunction: the proper drug for the proper patient.
Out of these 35 studies, 19 are concerned with cavernous nerve (CN) injury-associated ED while 10 with diabetes mellitus- (DM-) associated ED.
49 Changi South Avenue treatment of painful diabetic neuropathy with capsaicin 0.075 healthy eating 2 Singapore 486056. High blood pressure (NICE 2010) is fairly common in pregnancy affecting about one mum-to-be in 10. Here is an interview with Loren from 2010 where he explains the biochemistry of why autoimmune diseases such as MS arthritis and Type 1 diabetes might be made worse by grains beans dairy and in some people egg whites and tomatoes. Basic Metabolic Panel (8) Introduction: A Abnormal glucose levels can indicate diabetes or hypoglycemia (low blood sugar).
He qualified at Auckland Medical School with a post-graduate diploma in Occupational Medicine.
By choosing a patient with one of the diseases on the list of pathos we had to do I was able to cut down on the work. Diabetes Food Pyramid listing according to food group Be patient however with dogs that aren’t used to wearing boots as such may take some time for PATIENT EDUCATION INFORMATION INSULIN IMBALANCE Insulin Imbalance Insulin is secreted by the pancreas. It was the highest single-game rating for a Broncos rookie QB since John Elway posted a 117.
People with type 2 (usually non-insulin dependent) diabetes have an increased risk of developing colorectal cancer. Metabolic syndrome and type 2 diabetes have both reached epidemic proportions worldwide with the global adoption of the westernized diet along with increased consumption of fructose You might sometimes have low blood sugar while you are using insulin. This article aims to review recent studies that have elucidated the role of individual proteins in these insulin home diabetes test cvs nursing diagnosis goals for diabetes To maintain normal blood glucose, the pancreas secretes additional insulin hormone. As outlined in the other ED algorithms, some patients will have undergone extended evaluation and others will have forgone further assessment.
At the same time, under the effect of vacuum attraction, it can activate blood stasis, force prostate gland duct to open passively, suck glandular inflammatory secretions and metabolites out, so as to alleviate stress of prostate body, make blood circulation smooth and glandular recover to be normal.Pneumatic MassageThrough the alternating effect of vacuum attraction, the blood repeat slosh in the penile arteries and cavernosa that make permeability of capillary enhance and cell tolerance increase.
Adipose-derived SCs (ADSCs) were employed in 18 studies while bone marrow SCs (BMSCs) in 9.
I have been diagnosed with gestational diabetes and am looking for recipes to use as part of my gestational diabetes diet. Dogs with excess urinary glucose tend to excrete very large amounts of urine Learn the facts about diabetes and teeth and how it can affect your oral health. In addition to lifestyle measures the insulin-regulating drug metformin (Glucophage diabetes diary app type vitamin b12 1 generic) may Kombiglyze XR combines saxagliptin and metformin. It cures diabetes and ings the blood New insulin options are available so which should you turn to in diabetic dogs?
We treat each patient with care and confidentiality - you can relax in our clinic and enjoy your one-on-one consultation in a comfortable private setting. I can not wait… How cinnamon helps prevent medicare reimbursement for diabetes supplies diabetes. And the often heard name Taliban so hated and despised in America is viewed at least at first with joy; spoken in glowing terms and with hope. Mostly it’s about controlling what I can eating well getting full night sleeps and keeping up with my medication.
Chronic kidney disease (CKD) occurs over time and is usually defined as lasting over 3 months. As the disorder progresses, the pancreas weakens, and production of insulin diminishes until insulin injections may be necessary. While 50 % of men over 40 years of age have some degree of ED, less than 10 % ever seek treatment, presumably because many of them are not bothered by the ED and are capable of having satisfactory sexual relations despite their ED.
Transplantation of SCs was done mostly by intracavernous (IC) injection, as seen in 25 studies. Many studies demonstrate that persons with type 2 diabetes are at increased risk for heart disease.
Partners are welcome to attend the consultation, although we won't phone you or leave any messages if you specifically request that you are the only one to be contacted.
If you notice unusual behavior or have concerns you can talk to your child’s doctor diabetes educator or our social worker or child psychologist.
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Testosterone undecanoate improves erectile dysfunction in hypogonadal men with the metabolic syndrome refractory to treatment with phosphodiesterase type 5 inhibitors alone. With negative pressure, water or liquid medicine can massage penis repeatedly, so the instrument can strengthen the activity of penile skin cells and accelerate the decomposition of drug ion and absorption of cells to drug-ion. Allogeneic and xenogeneic transplantations have increasingly been performed but their immune-incompatibility issues were rarely discussed. See treatment testing blood glucose monitors test strips health care How to Save Money on Health Care. If you test eat and what diabetics diabetes symptoms with feet nick jonas and diabetes Outpatient Diabetes Management Guidelines should eat eye damage (retinopathy). Paltridge's hospital training was done in Auckland however he also worked in surgical out patients in a Thai hospital. An affected person may realize they are insulin resistant after many years when they develop type 2 diabetes.
The configuration (with power outlets on the top arranged in a circle on the front side Diabetes Hypertension Erectile Dysfunction in a line and on the sides seems really goofy at first but it is quite ingenious.
More recent studies also tend to use combinatory therapies by modifying or supplementing SCs with angiogenic or neurotrophic genes or proteins. This acid Type 1 Diabetes Self Diagnosis Icd 10 Mody helps in weight loss by maintaining insulin level allowing less absorption of fat and glucose in the body and also improving the metabolism process. The three most important elements of success in giving insulin injections are: Ensure that you have the right dosage of insulin. I now have questions to ask my doctors, to get an informed consent, which I must not have had before. But still, few studies actually investigated and none proved paracrine action as a therapeutic mechanism. Thus, based exclusively on functional outcome data shown in preclinical studies, two clinical trials are currently recruiting patients for treatment with IC injection of ADSC and BMSC, respectively.1.
The effectiveness of psychological interventions for the treatment of erectile dysfunction: systematic review and meta-analysis, including comparisons to sildenafil treatment, intracavernosal injection, and vacuum devices. Although not life threatening by itself, ED is a strong predictor of high-mortality diseases such as coronary artery disease and cardiovascular disease [2–5]. Clinical guidelines panel on erectile dysfunction: summary report on the treatment of organic erectile dysfunction. ED does directly and negatively impact the quality of life of the afflicted men and their spouse [6–11]. In a 1999 report the worldwide prevalence of ED was estimated to be 152 million men in 1995 and predicted to increase to 322 million men by 2025 [12].
Moreover, regardless of their therapeutic efficacy or inefficacy, all current treatment options treat only the symptoms, not the underlying causes, and most of them need to be taken by or administered to the patient when having an erection which is perceived as necessary. Thus, current research efforts are geared toward finding long-term solutions that can reverse the pathogenesis of ED and thereby restore the patient’s ability to achieve natural penile erection.
One of such research efforts is the investigation of stem cells (SCs) as therapeutic agents, and in this review article I will summarize and discuss all available relevant data in this field of research.2. Erectile Function Penile erection is a physiological process that involves the expansion and elongation of a paired cylindrical structure called corpora cavernosa (singular: corpus cavernosum, CC) that run the length of the penis [17].
Evaluating preference trials of oral phosphodiesterase 5 inhibitors for erectile dysfunction.
Inside each CC is a maze of miniscule chambers called sinusoids that are collapsed and occupy a minimal amount of space when the penis is in the flaccid state. When a man is sexually aroused, blood enters the sinusoids, resulting in their expansion and thus penile erection. When sexual stimulation subsides, blood exits the sinusoids, and the penis returns to the flaccid state.The cycle of sinusoidal expansion and collapse is locally controlled by smooth muscle cells (SMCs, or CSMCs as pertaining to CC), which form a multilayered structure as part of the sinusoidal wall [18, 19]. Erectile dysfunction: monitoring response to treatment in clinical practice–recommendations of an international study panel. When CSMCs are in a contracted state, blood flow into the sinusoids is kept at a minimum; when CSMCs transit to a relaxed state, blood flow into the sinusoids is increased, resulting in sinusoidal expansion. The cycle of CSMC contraction and relaxation is in turn controlled by two other tissue components inside the CC, namely, the cavernous endothelial cells (CECs) and the cavernous nerves (CNs).


CECs are located as a single layer of cells alongside the CSMCs inside each sinusoid, and together, CECs and CSMCs form the wall that defines each sinusoid [18, 19]. Hormonal testing and pharmacologic treatment of erectile dysfunction: a clinical practice guideline from the American College of Physicians. CNs, which arise from neurons in the inferior hypogastric plexuses in humans or in the major pelvic ganglia (MPG) in the rat [20, 21], track throughout the CC and end in the vicinity of CSMCs [18, 19].
Sexual stimulation causes CNs to release nitric oxide (NO), which enters nearby CSMCs, triggering their relaxation [22–24]. The subsequent increase of blood flow into the sinusoids induces shear stress on the CECs, triggering their release of NO. Oral phosphodiesterase-5 inhibitors and hormonal treatments for erectile dysfunction: a systematic review and meta-analysis. During erection, the increased blood flow into the sinusoids causes CC to expand and compress against the TA. Being a sturdy and resilient structure, the TA permits CC expansion, but with increasing resistance. As the tension between the expanding CC and the resisting TA increases, so does the overall penile rigidity. Furthermore, the compression of CC against TA causes the closure of subtunical veins that otherwise would allow the escape of blood from the sinusoids. Such a venous occlusive mechanism ensures that the CC remains fully engorged and the penis fully erect until the cessation of sexual stimulation [17].NO, which is critical for triggering CSMC relaxation, is formed within CECs and CNs by nitric oxide synthase (NOS) that catalyzes the conversion of L-arginine and oxygen to L-citrulline and NO [30]. While performing the same function in NO production, the endothelial NOS (eNOS) and the neuronal NOS (nNOS) are encoded by two separate genes [30].
More importantly, from a technical standpoint, eNOS and nNOS are sufficiently different in their protein sequences so as to permit the generation of their specific antibodies [31, 32]. In ED research, including many studies that will be discussed in this review, these antibodies have proven to be highly valuable for the assessment of ED-related changes in the cavernous endothelium and nerves.NO enters CSMCs by diffusion, and once inside, it activates the soluble guanylyl cyclase, which then catalyzes the conversion of GTP to cGMP [22, 23].
Meanwhile, existing cGMP is hydrolyzed by phosphodiesterases (PDEs), most notably, PDE5 [33, 34]. When cGMP concentration drops below a threshold level, PKG is deactivated and its downstream targets dephosphorylated, thereby returning CSMCs to the contracted state and the penis to the flaccid state [22, 23].3. Erectile DysfunctionThe worldwide prevalence of ED was estimated to be 152 million in 1995 and predicted to be 322 million by 2025 [12]. The organic type of ED is further classified into neurogenic, vasculogenic, cavernous, hormonal, drug-induced, and systemic disease-related [17].
For all published SC-for-ED studies, only the neurogenic, vasculogenic, and cavernous types are relevant. Specifically, in concern with neurogenic and vasculogenic types, the relevant studies focused on CN injury-associated and DM-associated ED, respectively. In particular, PDE5Is are currently the most prescribed treatment because of their ease of use (as orally taken pills) and overall proven efficacy [35]. Such high dropout rates for these two types of ED are not entirely unexpected, as an earlier study already identified them as least responsive to PDE5I treatment [14]. For other types of ED that have been investigated as SC treatment targets, only the TA injury-associated ED will also be discussed in detail in a separate section.
In a peer-reviewed publication that analyzed prior epidemiological studies totaling 370 country-years and 2.7 million participants, Danaei et al. Furthermore, in a forward-looking projection, the International Diabetes Federation estimated that by 2030 the number of people with DM worldwide will be 552 million [39]. Thus, the global diabetes epidemic is alarmingly real.DM is associated with a large assortment of complications, including ED. Diabetic men also tend to incur ED 10–15 years earlier and are 3 times more likely to have ED than nondiabetic men [41, 42]. Importantly, both the severity of ED and the impact on quality of life by ED are significantly greater in diabetic than in nondiabetic men [43, 44]. Thus, the identification of an effective treatment for DM-associated ED is one of the most important objectives of current ED research efforts.DM is a systematic disease that affects every part of the body.
In the penis, it is associated with reduced contents of all three key components for erectile function, namely, CN, CEC, and CSMC [45–49]. The reduction of CEC content is likely due to DM-induced apoptosis in CEC as demonstrated by immunohistochemical analysis of CC samples between diabetic and nondiabetic patients [50]. This clinical histological finding has recently been corroborated by a basic science study, which identified mitochondrial fragmentation and cellular apoptosis in CECs cultured in high glucose medium [32, 51]. Histological analysis of CC samples also identified a significantly higher apoptotic index in the CSMC of diabetic versus nondiabetic rats [52].
Similarly, the reduced penile CN content has been shown to be due to apoptotic cell death of nNOS-positive neurons in the MPG of diabetic rats [48]. Postprostatectomy and Postradiotherapy EDProstate cancer is the most common malignancy in men, with estimated numbers of new cases and related deaths being 217,730 and 32,050, respectively, in the USA in 2010 [53].
However, despite being highly effective, these treatments often incur after treatment complications, such as ED [55, 56]. However, despite the introduction of nerve-sparing RP 30 years ago, ED remains a frequent consequence of such surgeries [58, 59]. Therefore, it is now commonly believed that, although leaving the CNs intact, nerve-sparing RP still causes subtle changes that are not obvious to the surgeons [55, 60]. These changes cause CNs to undergo Wallerian degeneration and eventually lose their connection to the corpora cavernosa [56, 61]. Alternatively, the surgery-incurred insults may temporarily prevent the CNs from releasing NO into the CC, and without NO-induced engorgement, the penile tissue becomes hypoxic and its CSMC replaced by collagens [56, 60, 61]. However, while RP-associated ED has been intensively investigated at the basic science level, RT-associated ED is rarely studied [49]. Nevertheless, three independent studies have found that radiation over the lower abdomen in the rat caused reductions in erectile response and in CN and CSMC contents [49, 68, 69]. Thus, post-RP and post-RT ED appear to share a common pathological mechanism, that is, treatment-induced CN injury followed by CSMC atrophy.Similar to other types of ED, post-RP and post-RT ED are most commonly treated with PDE5Is [56].
However, as its name indicates, a PDE5I inhibits PDE5, which, by breaking down cGMP, terminates the NO-activated erectile signaling pathway [23, 33].
Therefore, when CNs are injured, as in the situation with RP or RT-treated patients, their ability to release NO into CC is compromised, and if there is no NO release into CC, erection would not occur, regardless whether PDE5 is inhibited or not. Thus, it is obvious that the effective treatment of post-RP and post-RT ED requires repair of the damaged CN, and this has been the goal of the majority of SC-for-ED studies, especially those published in the past two years.6. PD is characterized by the presence of a fibrous plaque (or plaques) in the TA that causes pain and deformity (curvature, narrowing, and shortening) in the erect penis [70]. PD therefore negatively impacts the patient’s sexual function and partner relationship [71].
Nevertheless, in serious scientific publications, PD is frequently described in the Introduction section as a disease that directly causes ED, with reference to a study by Lopez and Jarow [72].
Thus, the authors concluded that, when compared to abnormal arterial blood flow, veno-occlusive dysfunction was the principal cause of ED in PD patients.
However, it should be noted that the study never examined whether PD (TA plaque) caused veno-occlusive dysfunction or ED. In another study that evaluated 143 PD patients, only 27 (19%) were found to have concomitant ED, and 22 (including 4 diabetics) of the 27 PD+ED patients were found to have veno-occlusive dysfunction [73].
Importantly though, neither study provides evidence that PD (TA plaque) caused veno-occlusive dysfunction or ED. In fact, in an earlier study only 18 out of 62 PD patients (29%) were found to have concomitant ED, and 17 out of these 18 PD+ED patients were further identified as having some underlying diseases (such as DM) that contributed to their ED [74]. Therefore, none of these three studies provides evidence that PD (TA plaque) is a direct cause of ED in PD patients. Finally, in the only animal study that attempted to answer why PD patients suffer from ED, PD was simulated in the rat by injection of transforming growth factor- (TGF-) into the TA (to induce fibrosis) or by surgical incision in the TA (to cause trauma) [75]. Six weeks later both groups of rats were found to have altered TA histology and lowered erectile response when compared to sham-treated rats. Therefore, this study appears to have obtained evidence that TA abnormalities can cause ED, but the question remains whether treatment of PD can result in the restoration of erectile function.Plaque excision followed by patch grafting is a common surgical procedure for the correction of penile deformities in PD patients [76]. However, in spite of its proven efficacy, postsurgical complications such as ED can occur [77]. Therefore, various approaches, including the use of novel graft materials, have been investigated toward minimizing the occurrence of these complications [76].
In a recent animal study, porcine small intestine submucosa (SIS), which has already been used for TA reconstruction in PD patients, was seeded with adipose-derived stem cells (ADSCs) and then grafted into incised rat TA to see if ADSC seeding can reduce the incidence of postsurgery ED [78].
In another recent animal study [79] ADSC was injected into the TA of TGF--induced PD rats to see if ADSC can reduce the severity of ED. Current State of Stem Cell Therapy for Erectile DysfunctionThe first SC-for-ED study was published in 2004, and since then, up to November 2013, there have been a total of 34 additional studies in this field of research (Table 1). While 15 of these studies were published between 2004 and 2011, 20 were published after 2011. In any event, among all 35 studies, 19 chose CN injury-associated ED as the disease target, and 18 employed ADSC as the therapeutic cell type (Table 1). While that study was carried out in Korea, two clinical trials have been approved in France and the USA and are currently recruiting patients.
The French trial (Identifier: NCT01089387) is a phase I-II trial and will test the safety and benefit of IC injection of autologous bone marrow mononucleated cells (BMMNC) in post-RP ED patients. While most of these businesses are located in developing countries such as the Philippines and Thailand, some indicate their presence in the USA.
This is surprising because for-profit SC treatment of any disease is illegal in the USA, and criminal convictions have been handed down on cases that involved treating patients with SCs. In any event, SC therapy for ED remains largely in the preclinical investigational stage, and this is what will be discussed in the following sections.8. Animal ModelsAll but one preclinical SC-for-ED studies used rats as animal models; the singular exception used mice (Tables 2, 3, and 4). Aging animal models were used in 3 studies (Table 2), and they were rats between 20 and 30 months of age.
The high cost of this diet and the lengthy time requirement are hindering factors for this model’s widespread usage. TA injury animal models were used in two studies (Table 2), and they were established by two different procedures.
As such, this animal model should probably be called a TA reconstruction rather than a TA injury ED model. In the later study, TA injury was induced by injection of 50 g of TGF- into the TA, and one day later, ADSC was injected into the same site as a treatment for the injured TA. The ease of this DM-induction procedure is certainly the main reason why this animal model is frequently used in research despite the fact that only 5% of DM patients are type 1. On the other hand, only one study has used T2DM animal model—the Zucker Diabetic Fatty (ZDF) rat.
To simulate post-RP ED, the investigator performs a lower abdominal incision and, with the aid of a dissecting microscope, identifies the two branches of CN, which arise from the MPG and course proximally on both sides of the prostate and distally alongside the urethra toward the penis. Crush is commonly done by applying a hemostatic clamp to the CN so as to simulate accidental nerve contusion or traction that occurs during nerve-sparing RP. Freezing is commonly done by applying a cryoprobe to the CN so as to offer another way of preserving nerve structural continuity.
Both transection (a simple cut) and resection (removal of a CN segment) can be considered as representing nonnerve sparing RP, but transection is more likely to allow nerve reconnection than resection is.
These studies used similar procedures but with slightly different dosage, duration, and frequency of radiation. These modifications resulted in no death, yet achieving the goal of inducing ED in the irradiated rats.
Thus, some adjustments appear to be necessary for each research group to produce the optimal post-RT ED animal model.9. Stem Cell BasicsSCs can be classified according to their differentiation potential into pluripotent and multipotent, where pluripotent signifies the potential to differentiate into all cell types, whereas multipotent, some but not all cell types. SCs can also be classified according to their source into embryonic (ESC) and adult (ASC), where embryonic indicates the inner cell mass of a blastocyst, whereas adult, various tissues of a developed or developing individual. However, many studies, including several in ED field, have stated that SCs isolated from adult tissues are pluripotent. This misunderstanding is a result of accepting in vitro differentiation data that were generated by using nonphysiological conditions and nonspecific cell markers (see below for further details).
In any event, depending on their tissue origin or the tissue type they can differentiate into, ASCs can be further classified into hematopoietic, neural, epithelial, and mesenchymal.
Because mesenchymal SCs (MSCs) are by far the most frequently used cell types in SC-for-ED research, some of their characteristics relevant to ED research are discussed below.MSCs have the potential to differentiate into mesenchymal tissues, such as bone, cartilage, and fat. They were first identified in the bone marrow but have now been shown to exist in virtually all postnatal tissues, including skeletal muscle and adipose tissue [115, 116]. Since then, several other research groups and a more recent study of ours have confirmed the adventitial localization of ADSCs [118–122]. Based on this definition, VSCs can differentiate into pericytes, smooth muscle, and endothelial cells, which are then assembled into mature blood vessels, during angiogenesis or neovasculogenesis within any particular tissue.
However, up to this date, it remains controversial whether cellular differentiation is truly responsible for MSC’s therapeutic efficacy. First, it is important to know that virtually all claims of MSC’s differentiation potential are based on in vitro evidence. In fact, the International Society for Cellular Therapy (ISCT) recommended using chemical or immunohistochemical (IHC) staining of cultured MSCs as a means to demonstrate their differentiation potential [124]. As such, while numerous MSC studies have fulfilled this in vitro criterion, relatively few have investigated whether MSCs do indeed differentiate into particular cell types after transplantation into a host.
In the few studies that did conduct such investigations, the results are either utterly negative or kind-of positive [125]. However, all three recommended positive markers, CD105, CD73, and CD90, are expressed in a wide variety of cells while one of the recommended negative marker, CD34, has proven to be highly useful for the identification and isolation of several MSC types, particularly, ADSCs [127].
In fact, CD34+ bone marrow cells were used to generate the Stro-1 monoclonal antibody [128, 129], which has since been used in hundreds of studies for the identification and isolation of a wide variety of MSC types [130, 131].
Specifically, MSCs have been shown to secrete trophic and immunomodulatory factors that have the potential to (1) stimulate local tissue regeneration, (2) modulate local and systematic inflammatory responses, and (3) mobilize host cells, particularly bone marrow SCs (BMSCs), as repair cells for injured tissues. However, while gaining increasing acceptance, the paracrine theory raises an obvious question: Why not just use the paracrine factors as therapeutic agents? The answer may lie in the fact that MSCs are live cells and therefore capable of responding to host tissue needs, and their paracrine repertoire is obviously much larger and more diverse than single factors.
Nevertheless, just like cellular differentiation, paracrine action as a mechanism for MSC’s therapeutic effects remains largely unproven. Embryonic Stem CellESC has been used in only one SC-for-ED study, and it is the first SC-for-ED study (published in 2004) [94]. The study was conducted in our laboratory and was a very challenging task mainly because of the difficulty in establishing rat ESC in culture [135–137].
In any event, while we finally succeeded in establishing the culture and demonstrated its therapeutic efficacy, ethical concerns about using embryos as a source of therapeutic cells and the emergence of MSCs as substitutes led us to begin exploring ADSC as a more clinically feasible therapeutic agent.
In any event, BMSCs have been investigated in thousands of studies, including 9 SC-for-ED studies, with overall proven therapeutic efficacy. However, it should be noted that in preclinical studies that use small animals as cell donors, the isolation of BMSCs is commonly done after sacrificing these animals.
Therefore, transplantation of BMSCs in such studies is mostly allogeneic and sometimes xenogeneic.


This would of course raise immunocompatibility issues, but such issues are rarely addressed. Bone Marrow Mononuclear CellA preclinical ED study employed BMMNCs to treat CN injury ED [96]. The cells were harvested from donor rats and injected into ED rats without characterization; therefore, their relevance to SC research cannot be determined with certainty.
Thus, despite lacking experimental evidence for SC relevance, the study is included for discussion in this SC-focused review article.
Endothelial Progenitor CellEndothelial progenitor cell (EPC) has been used or claimed to have been used in one SC-for-ED study [86]. In recent years, both its relevance to ED and its identity as a SC type have been controversial.
In regard to its ED relevance, several studies have shown that ED patients had a reduced number of circulating EPC [141–145], and another study even suggested that boosting EPC number through dietary supplementation could enhance erectile function [146]. These latter studies thus suggested that the discrepancy might be due to differences in the immunophenotypes that were used to evaluate the identity of the isolated EPCs. However, the actual reason is more likely due to uncertainties about what EPC really is [150, 151]. For example, it has been shown that EPC might be monocytes contaminated with platelet microparticles [152], or they might be injured or senescent vascular endothelial cells that slough into the bloodstream [153]. Umbilical Cord Blood Stem CellUmbilical cord blood SC (UCBSC) has been used in only one SC-for-ED study, and it is a clinical study, the only published clinical study [80]. However, umbilical cord blood is known to contain both hematopoietic and mesenchymal SCs [158], and based on the following considerations, the UCBSC in this study is most likely MSC.
First, the cells were provided by a company (also partaking in the study) that commercializes umbilical cord blood-derived MSCs. Skeletal Muscle-Derived Stem CellThree ED studies have used skeletal muscle-derived stem cells (SkMSCs) as treatment cells.
The first study isolated such cells from rats [95] while the two more recent studies from mice [82, 103].
These cells were all used to treat ED in rat models; therefore, the transplantation was xenogeneic in the two more recent studies. And, several urology-related papers that employed rat SkMSCs were also published earlier, including two that were published 7 years earlier [160, 161].
Only cells that do not adhere in one particular round are seeded in the next round, because early adhering cells (1st and 2nd rounds) have been shown to be more fibroblastic whereas late adhering cells (5th and 6th rounds) more myogenic [160, 161]. Adipose-Derived Stem CellADSC is now the most frequently used cell type in SC-for-ED research, with 18 studies versus 9 for the second-place BMSC. The principal reasons for such an increased interest in ADSC are (1) its overall proven similarities with BMSC, (2) its overall proven therapeutic efficacy across medical disciplines, (3) its abundant tissue source, (4) its ease of isolation, and (5) the availability of automated isolation devices.The first demonstration of adipose-derived stromal cells as SCs is generally credited to a study published in 2001 by Zuk et al. The SVF, which appears as a pellet in the centrifuge tube, contains endothelial cells, smooth muscle cells, pericytes, fibroblasts, mast cells, and preadipocytes [170]. Thus, the relationship between SVF cells and ADSCs is similar to that between BMNNCs and BMSCs, as discussed earlier.While cultured ADSCs have been used in most SC-for-ED studies, uncultured SVF cells have been increasingly tested as therapeutic agents. The reasons are mainly the emergence of machines that can rapidly process a human lipoaspirate into SVF cells and reports that such cells are as effective as ADSCs in experimental therapies.
Testis-Derived Stem CellA recently published study demonstrated the isolation of SCs from human testis [111]. These cells were positive for CD34 and localized to the testicular stroma; therefore, they are most likely MSCs.
However, while it would seem more logic to use these cells for infertility treatment, the study chose CN injury ED instead. In any event, the authors stated that these cells might represent a promising new autologous cell source for clinical use. But, it remains to be seen whether patients will be willing to sacrifice portions of their testicles for the treatment of their ED.11. Stem Cell ModificationA few studies have tested SCs that were transduced or transfected with genes known to encode proteins that positively regulate erectile function [81, 86, 88, 92–94, 102]. Transfection with plasmids results in cells that only transiently express the transfected gene while transduction requires using a viral vector and a lengthy process to select for positively transduced cells [172]. Therefore, the implementation of transfected or transduced SCs in clinical trials will require preclinical demonstration of highly significant benefits when compared to their untransfected counterparts. Stem Cell LabelingFor the purpose of tracking SCs after their transplantation, various compounds or genes have been used as cell labels. However, every label has its shortcomings, as discussed in detail in our recent review [126]. Briefly, the use of LacZ gene, which encodes bacterial -gal, is hampered by endogenous expression of -gal in mammalian tissues. The use of GFP gene, which encodes a green fluorescence protein, is troubled by autofluorescence in mammalian tissues. DAPI, a DNA labeling dye, binds DNA noncovalently; therefore, it can leak from transplanted cells to host cells. DiI, a cell membrane labeling dye, binds to cell membrane noncovalently; therefore, it can also leak from transplanted cells to host cells. Therefore, cellular proteins can no longer be detected by IHC or immunofluorescence (IF) due to loss of antigenicity.
EdU is a newer thymidine analog that requires no special tissue treatment for detection; therefore, costaining by IHC or IF for cellular proteins is feasible. However, similar to the situation with BrdU, long-term detection of transplanted cells is possible only if the cells are relatively quiescent, as the label gets diluted with each round of cell replication.13. ImmunocompatibilityIn preclinical studies that employ rats or mice as disease models, transplantation of SCs is most commonly allogeneic.
This is due to the following: (1) allogeneic transplantation requires SC isolation from as few as one animal whereas autologous transplantation requires SC isolation from each test animal and (2) vital tissues such as bone marrow and skeletal muscle cannot be harvested in sufficient quantities for autologous SC preparation without seriously harming the animals. In the case with ADSC, despite its more abundant harvestable tissue source than BMSC or SkMSC, increasingly more studies are conducting xenogeneic transplantation, nonetheless, and the donor species has been exclusively humans [173]. The reason is obviously the high availability of adipose tissues that are removed from millions of patients who elect to undergo liposuction or lipectomy. In any event, whether allogeneic or xenogeneic, studies that performed such transplantations usually do not talk about the immunocompatibility issue [173]. For example, we have recently published a review article on MSC’s immunocompatibility issues [173], and although the MSC in question is ADSC, the discussion is actually applicable to all MSCs. This review article itself or some of its referenced studies can be cited to explain why MSCs can be transplanted allogeneically or xenogeneically in immunocompetent recipients without the use of immunosuppressants. Briefly, MSCs have been rather consistently shown to possess immunosuppressive and immunomodulatory properties, and there is also convincing evidence that MSCs do not express major histocompatibility complex-II and therefore elicit no immune reaction when transplanted allogeneically or xenogeneically. In this study, 30 patients with ischemic cardiomyopathy were equally randomized into an allogeneic and an autologous groups for transendocardial BMSC injection. Stem Cell TransplantationIC injection of erectogenic agents is a well-established method to induce erection in ED patients; therefore, in the first SC-for-ED study we tested whether IC injection of SCs could treat CN injury ED in rats [94]. As the results showed that both transplantation routes were equally effective in treating CN injury ED, and due to the fact that IC injection is easier to perform than intra-MPG injection, IC injection has become the preferred method for the transplantation of SC into CN-injury and other types of ED animal models (25 out of 35 studies). Such therapeutic mechanisms have received supports from our studies that showed (1) IC injected ADSCs can migrate to the MPG in response to CN injury [101, 175], (2) cultured ADSCs abundantly secrete CXCL5 cytokine, and (3) CXCL5 possesses both angiogenic and neurotrophic properties [176, 177].As intra-MPG injection is less clinically feasible than IC injection, it has not been used again until recently in which CN injury ED was the treatment target [102]. While positive outcomes were reported, no reason was given as to why choosing this more difficult injection method. In any event, the same group of researchers also tested other transplantation methods in three additional CN injury ED studies.
Specifically, SCs were applied to the injured CNs and then covered with a scaffold material of either poly(lactic-co-glycolic acid) (PLGA) or hydrogel [104, 107, 108].
While positive outcomes were observed, it is presently unknown whether this scaffold approach is better than IC injection in terms of treatment efficacy. In three other CN injury-ED studies by two other research groups, SCs were injected periprostatically with [109, 110] or without [111] concomitant IC injection. Direct comparison showed that periprostatic and IC injections produced similar therapeutic effects, but concomitant periprostatic and IC injections did not produce better outcomes than either injection alone [110].Autologous nerve graft has been tested for the repair of damaged CN [178, 179].
Thus, in a recently published study we tested whether acellular matrix seeded with SCs can be used as a nerve graft for CN repair [99]. Grafting of the seeded matrix to repair resected CNs resulted in improved erectile function that slightly missed statistical significance (, due to large variations). Thus, we believe that the approach is feasible but requires improvements in fabrication of the acellular matrix.We have previously shown that both intraorgan (urinary bladder or urethra) and intravenous (IV) injections of ADSCs improved urinary function in rat models of stress urinary incontinence and detrusor overactivity [180, 181]. In a more recent study we showed that IV injection of ADSC also improved erectile function in post-RT ED rats [105].
Thus, IV injection appears to be a feasible option for SC transplantation.TA reconstruction with grafts is often performed on PD patients with large plaques. In a recent study, TA reconstruction with ADSC-seeded SIS was found to have a lower rate of ED complication than using unseeded SIS [78].
In another recent study, ADSC was injected into the TA that was undergoing fibrotic changes due to a prior TGF- injection [79]. This intratunical ADSC injection resulted in significantly less TA fibrosis and better erectile function when compared to intratunical saline injection.15.
Functional AssessmentWhether SC treatment improves erectile function is most commonly assessed at 4 weeks after treatment by measurement of intracavernous pressure (ICP) in response to electrostimulation of CN. Such stimulation mimics sexual stimulation and causes an increase of ICP that can approach systemic blood pressure.
In fact, to account for variations in individual animal’s systemic blood pressure, ICP is often normalized to mean arterial pressure (MAP). The MAP and ICP values are acquired via a pressure transducer connected to a data acquisition system. Electrostimulation is applied through a stainless steel bipolar hook placed on the CN approximately 5 mm distal to the MPG. Histological AssessmentThe above-described functional assessment requires laparotomy followed by sacrificing the animal. The sacrificed animal is then subjected to the harvest of the penis, MPG, and any other tissues of interest.
In the penis, IHC or IF staining is routinely used to assess the three key structures that regulate penile erection, namely, CEC, CSMC, and CN.
CN is mostly commonly evaluated by IHC or IF staining for the expression of nNOS in the dorsal nerves. However, we have recently reported that staining with Alexa fluor-conjugated phalloidin was easier and quicker, and the resulting images were superior [18].
Masson’s trichrome staining has also been commonly used to assess CSMC although the resulting red stains actually represent not only CSMC but also CEC, fibroblasts, and any other cells.
For PD-related studies, the assessment of TA is usually done by trichrome staining or by IHC or IF staining for collagen-I and elastin. For studies using CN injury models, the examination of MPG is usually accomplished by IHC or IF staining for S100, neurofilaments, or other neural markers.A few earlier SC-for-ED studies have attempted to identify transplanted SCs through histological examination of penile tissues. However, molecules or agents that were used to prelabel SCs all have inherent shortcomings [126].
In addition, we have shown that IC transplanted SCs quickly disappeared from penile tissues [101, 175]. Main Outcomes Up to November 2013 a total of 35 SC-for-ED studies have been published, and 29 of them are concerned with either CN injury (19 studies) or DM (10 studies).
Diabetic EDThe first such studies were published in 2010, both dealing with T2DM, with one being clinical trial and the other preclinical. The clinical trial was carried out in Korea and involved treating each of seven T2DM patients (57 to 87 years of age) with IC injection of 15 million allogeneic UCBSCs [80]. At one month after treatment, three patients regained morning erection, and at 3 months, three additional patients regained morning erection. However, despite having increased penile rigidity, these patients were still unable to achieve vaginal penetration unless taking sildenafil before coitus. Nevertheless, at 11-month follow-up, one patient was able to maintain sufficient erection for coitus. Interestingly, all patients except the oldest had reduced levels of blood glucose and glycosylated hemoglobin, suggesting SC therapy might have antidiabetes effects, and supporting our observation that IC injection is a systemic application (see Stem Cell Transplantation).The preclinical study was conducted by our group [85] and it utilized the ZDF rats, which were found to develop T2DM within the first 10 weeks of age and to develop ED at 22 weeks of age.
These T2DM-ED rats were randomized for treatment with IC injection of autologous ADSC or with saline. Histological examination of erectile tissue also found that ADSC-treated rats had lower levels of apoptosis and higher numbers of endothelia cells and nNOS-positive nerves.Apart from the two studies mentioned above, all SC-for-diabetic ED studies employed STZ-induced T1DM animal models. In 2012, the same team of researchers published a similar study, this time adding a group of rats treated with VEGF-transduced BMSC [88]. Thus, this discrepancy needs to be resolved before a conclusion can be made on whether VEGF transduction indeed improved therapeutic efficacy.Three additional studies were published in 2012.
While 10,000 cells had no effects, 100,000 and 200,000 improved ICP to 82% of normal control. Such data is valuable in that they validated the importance of SC and identified a potential optimal dosage.Two studies were published in 2013. CN-Injury EDThe first such study transplanted BDNF-transduced ESC into a CN crush injury rat model by either IC or intra-MPG injection [94]. While both treated groups were significantly better than the untreated group, there was no significant difference between the two treated groups.
Histological analysis outcomes paralleled erectile functional outcomes.The second study transplanted allogeneic SkMSC into a CN transection injury rat model by IC injection [95]. Functional analyses at 2 and 4 weeks both showed significantly better ICP values in treated versus untreated groups. The third study transplanted allogeneic BMMNC into a 5 mm CN resection injury rat model by IC injection [96]. Functional analyses at 3 and 5 weeks both showed significantly better ICP values in treated versus untreated groups.Two CN crush injury studies were published in 2010. One emphasized on comparing between allogeneic BMSC and a specific population of allogeneic BMSC that was selected for cell surface expression of p75 low affinity nerve growth factor receptor (p75LNGFR) [98]. The other was interested in comparing between autologous ADSC and cell lysate that was prepared from autologous ADSC [97].
Functional and histological analyses at 4 weeks showed that p75LNGFR-selected BMSC was significantly better than unselected BMSC, and ADSC and ADSC lysates were equally effective in treating CN crush injury ED. One is similar to the abovementioned 2006 study [95], as acknowledged in its discussion, in that the same animal model (CN transection), same SC type (SkMSC), and same injection route (IC) were employed, and similar functional outcome (ICP value) obtained [100].
The other is unique in that SC was employed as seeded cells on an acellular matrix, which was then grafted to repair a 5 mm gap in resected CNs [99].
The functional outcomes were favorable but slightly missed statistical significance.Six CN injury studies were published in each of 2012 and 2013. Third, for the first time we showed that IC injection of SCs (autologous SVF cells in this case) was able to treat both acute (immediate) and chronic (4 weeks) CN injury-induced ED [106]. This study is also the first to examine functional and histological outcomes at 3 months post-SC injection, instead of the more commonly chosen one-month time point.The remaining three 2012 studies all investigated combinatory SC therapy.




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