A review of the treatment of male pattern hair loss

Introduction: Androgenetic alopecia is a common hair loss disorder affecting up to 80% of males by the age of 80. It is characterized by androgen related progressive thinning of hair in a defined pattern. It results in diminished self-esteem, reduced confidence and distress in affected men, irrespective of age or stage of baldness. An effective treatment for hair baldness is needed.Areas covered: In androgenetic alopecia, hair follicles undergo progressive miniaturization. Genetic factors and androgens are key role-players in disease pathogenesis. Herein the authors review the pharmacologic treatment of androgenetic alopecia, which involves 5 alpha reductase inhibitors, minoxidil and prostaglandins. Non-pharmacologic approaches are also explored.Expert opinion: Androgenetic alopecia progresses over time and although the current available medical treatments like finasteride and minoxidil are effective in arresting the progression of the disease, they allow only partial regrowth of hair at its best. Early treatment achieves a more optimal outcome. Non-pharmacologic treatments like PRP can be considered in patients refractory to medical treatment.Abbreviations: MPHL: male pattern hair loss; AGA: androgenetic alopecia; DHT: dihydrotestosterone; 5AR: 5-alpha-reductase; VEGF: vascular endothelial growth factor; PG's: prostaglandins (PG's); PGD2R: prostaglandin D2 receptor; VPA: valproic aid; SR: Serenoa Repens; PRP: platelet-rich plasma; PDGF: platelet derived growth factor; TGF: transforming growth factor; ERK: extracellular signal-regulated kinase; PKB: protein kinase B; LLLT: low-level laser therapy; ROS: reactive oxygen species; RCT: randomized control trial; SFRP1: secreted frizzled related protein 1; DP: dermal papilla; PDE5: phosphodiesterase 5.

Short-term dietary protein supplementation improves reproductive performance of estrous-synchronized ewes when there are long intervals of prostaglandin or progesterone-based treatments for timed AI.

To evaluate the reproductive effects of a short-term dietary protein supplementation (Days -10 to -3) before timed AI (TAI = Day 0), 471 Merino ewes grazing native pastures were estrous-synchronized when there were either long intervals between prostaglandin administrations (two prostaglandin injections 15 or 16 d apart; PG15 and PG16, respectively) or with a progesterone-eCG (P4-eCG) protocol, resulting in a 3 × 2 experimental design. Ovulation rate on Day 8 (OR), non-estrous-return to Day 21 (NRR21), and fertility, prolificacy and fecundity on Day 70 were evaluated. The interaction between estrous synchronization protocol and supplementation was not significant for any of these variables (P > 0.05). Supplementation increased OR, prolificacy and fecundity (+0.14, +0.15 and +0.14, respectively, P < 0.01), but did not affect NRR21 or fertility of ewes (+6.2% and +6.7% respectively, P > 0.05). Ewes treated using the PG15 and PG16 protocols had a lesser OR (-0.27), prolificacy (-0.22) and fecundity (-0.20) than ewes treated using P4-eCG protocol (P < 0.01 for each), and similar NRR21 and fertility (-5.4% and -7.9% respectively, P > 0.05 for both variables), without significant differences between the PG15 and PG16 groups. In conclusion, a short-term dietary protein supplementation before TAI improved OR, prolificacy and fecundity of ewes which were estrous-synchronized by imposing long interval PG (15 or 16 d apart) or P4-eCG-based protocols. There was a greater OR, prolificacy and fecundity when there was use of the P4-eCG compared to long interval PG-based protocols. Estrous-non-return rate after AI and fertility as a result TAI were not affected by either the supplementation or the estrous synchronization protocols used.

Omega-3 fatty acids: a novel resort against gastrointestinal injury.

The integrity of gastric barrier derives from the balance between defending and damaging factors. In particular, prostaglandins play a relevant role in the maintenance of gastric homeostasis and prevention of peptic disease, at different levels. Omega-3 fatty acids, particularly eicosapentanoic acid, are the precursors of the third series of prostaglandins (with anti-inflammatory properties), also reducing the formation of the second series of prostaglandins (pro-inflammatory ones). Such a pathophysiological rationale brought to the experimental application, both in animal models and, more recently, in humans, of omega-3 fatty acids against gastrointestinal damage. Omega-3 fatty acids have shown interesting results in preventing different types of gastric damage in mouse models. A large retrospective case-control study on patients taking both anti-thrombotic therapy and eicosapentanoic acid showed (although only at unadjusted analysis) an inverse correlation between consumption of eicosapentanoic acid and gastrointestinal injury. Prospective, well-designed, comparative studies are warranted to clarify if omega-3 fatty acids may represent, or not, a novel resort against gastrointestinal injury.

Protein supplementation during a short-interval prostaglandin-based protocol for timed AI in sheep.

The aim of this experiment was to improve the reproductive performance of a short-interval prostaglandin (PG)-based protocol for timed artificial insemination in sheep, using a short-term nutritional treatment. During the breeding season (March-April), 132 multiparous and 61 nulliparous Corriedale ewes grazing natural pastures (600 kg DM/ha, 8.5% CP), were allocated to two groups: 1, Control group (n=100) two injections of D-Cloprostenol (75 µg per dose, 7d apart: Synchrovine(®) protocol); and 2, Supplemented group (n=93) ewes in which stage of the oestrous cycle was synchronised with Synchrovine(®) protocol plus focus feeding of a protein supplement (33.8% CP) between PG doses (Day -7 to -2). Cervical AI was performed at fixed time (Day 0), 46 ± 1.0 h after the second PG injection using 150 million sperm per ewe. Ovulation rate (Day 10), pregnancy rate, prolificacy and fecundity at Day 69 were evaluated by ultrasonography. Ovulation rate at Day 10 (1.20 ± 0.05 vs. 1.22 ± 0.05), pregnancy (46 ± 0.05 vs. 56 ± 0.05), prolificacy (1.09 ± 0.04 vs. 1.06 ± 0.05), and fecundity (0.49 ± 0.06 vs. 0.59 ± 0.06) at Day 69, were similar between groups (P>0.05; Control and Supplemented group respectively). It is concluded that focus feeding for 6d with protein supplementation during a short-interval PG-based protocol (Synchrovine(®)) did not improve the reproductive outcome associated with this protocol.

Nonoperative treatment for lumbar spinal stenosis with neurogenic claudication.

BACKGROUND: Lumbar spinal stenosis with neurogenic claudication is one of the most commonly diagnosed and treated pathological spinal conditions. It frequently afflicts the elderly population. OBJECTIVES: To systematically review the evidence for the effectiveness of nonoperative treatment of lumbar spinal stenosis with neurogenic claudication. SEARCH METHODS: CENTRAL, MEDLINE, CINAHL, and Index to Chiropractic Literature (ICL) databases were searched up to June 2012. SELECTION CRITERIA: Randomized controlled trials published in English, in which at least one arm provided data on nonoperative treatments DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. Risk of bias in each study was independently assessed by two review authors using the 12 criteria recommended by the Cochrane Back Review Group (Furlan 2009). Dichotomous outcomes were expressed as relative risk, continuous outcomes as mean difference or standardized mean difference; uncertainty was expressed with 95% confidence intervals. If possible a meta-analysis was performed, otherwise results were described qualitatively. GRADE was used to assess the quality of the evidence. MAIN RESULTS: From the 8635 citations screened, 56 full-text articles were assessed and 21 trials (1851 participants) were included. There was very low-quality evidence from six trials that calcitonin is no better than placebo or paracetamol, regardless of mode of administration or outcome assessed. From single small trials, there was low-quality evidence for prostaglandins, and very low-quality evidence for gabapentin or methylcobalamin that they improved walking distance. There was very low-quality evidence from a single trial that epidural steroid injections improved pain, function, and quality of life, up to two weeks, compared with home exercise or inpatient physical therapy. There was low-quality evidence from a single trial that exercise is of short-term benefit for leg pain and function compared with no treatment. There was low and very low-quality evidence from six trials that multimodal nonoperative treatment is less effective than indirect or direct surgical decompression with or without fusion. A meta-analysis of two trials comparing direct decompression with or without fusion to multimodal nonoperative care found no significant difference in function at six months (mean difference (MD) -3.66, 95% CI -10.12 to 2.80) and one year (MD -6.18, 95% CI -15.03 to 2.66), but at 24 months a significant difference was found favouring decompression (MD -4.43, 95% CI -7.91 to -0.96). AUTHORS' CONCLUSIONS: Moderate and high-quality evidence for nonoperative treatment is lacking and thus prohibits recommendations for guiding clinical practice. Given the expected exponential rise in the prevalence of lumbar spinal stenosis with neurogenic claudication, large high-quality trials are urgently needed.

Efficacy of ozone and other treatment modalities for retained placenta in dairy cows.

Retained placenta is a worldwide recognized clinical condition in puerperal cows, which can significantly affect their health and fertility. Available treatment modalities are often of questionable efficacy or associated with time constraints, practicality or monetary considerations for their wide application in a routine dairy practice. The objective of this study was to compare and assess the efficacy of different treatment options, including a novel ozone treatment, for the retained placenta. Two hundred cows diagnosed with retained placenta were divided into five treatment groups, each receiving a different treatment option. Group A (n = 40) was given a combination treatment of intrauterine ozone and parenteral cephalexin; group B (n = 40) was given intrauterine ozone; group C (n = 40) was given a combination of parenteral cephalexin and intrauterine antibiotic tablets; group D (n = 40) was given only parenteral cephalexin and group E (n = 40) was given parenteral prostaglandins in 11-day intervals. The control group (group Z, n = 200) included cows that gave birth without assistance and were not diagnosed with a retained placenta. The ozone treatment (groups A and B) was found to be the most effective modality resulting in the shortest period of days open, the smallest number of artificial inseminations until pregnancy, the smallest number of animals diagnosed with fever within 10 days post-calving, the highest percentage of animals pregnant within 200 days after calving and the smallest number of animals culled because of infertility, when compared to the other treatment groups. The intrauterine ozone flush therefore has a potential as an efficacious and cost-effective treatment option for retained placenta, with an overall positive effect on puerperal health and fertility in cows.

Practical considerations for the pharmacotherapy of pulmonary arterial hypertension.

Pulmonary arterial hypertension is a devastating disease. Before the 1990s, when pharmacologic treatment was finally approved, only supportive therapy was available, consisting of anticoagulation, digoxin, diuretics, and supplemental oxygen. Calcium channel blocker therapy was also an option, but only a small percentage of patients respond to it. However, starting with epoprostenol in 1996, the number of drugs approved to treat pulmonary arterial hypertension increased. Three distinct classes of drugs were developed based on the pathophysiology of the disease: the prostanoids, endothelin-1 receptor antagonists, and phosphodiesterase type 5 inhibitors. The prostanoids are administered either parenterally or by inhalation to replace the lack of prostacyclin within the pulmonary arterial vasculature. The endothelin-1 receptor antagonists were the first class of oral drugs to be developed, but drug interactions and adverse effects are prominent with this class. The phosphodiesterase type 5 inhibitors increase the second messenger cyclic guanosine monophosphate (GMP) that is induced by nitric oxide stimulation. All of the drugs within these three classes are distinct in and of themselves, and their clinical use requires in-depth knowledge of pulmonary arterial hypertension and its pathophysiology. Because these drugs have different mechanisms of action, combination therapy has shown promise in patients with severe disease, although data are still lacking. This article should serve as a practical guide for clinicians who encounter patients with pulmonary arterial hypertension and the drugs used for the treatment of this devastating disease.

Targeted approaches to the treatment of pulmonary hypertension.

Pulmonary arterial hypertension is a progressive and incurable disease. Over the past two decades, significant advances have been made in understanding and thus managing this disease. Multiple therapeutic options are currently available and optimizing the treatment of pulmonary arterial hypertension has become complex. Patients who meet the American College of Chest Physicians criteria for vasoresponsiveness can be safely and effectively treated with high-dose calcium channel blockers but require close follow up to assure durability of response. Patients with World Health Organization (WHO) functional class IV status and those with determinants of high risk for progression and death should be treated with an infused prostanoid agent without delay. These patients should also be referred early after stabilization for transplant evaluation. Patients with WHO functional class II status benefit from early initiation of oral therapies. Those with WHO functional class III status and lower determinants of risk for progression may receive treatment with one or more oral or inhaled agents, though many experts would advise early use of infused prostanoids for these patients as well.

Low concentrations of resveratrol potentiate the antiplatelet effect of prostaglandins.

Resveratrol, a polyphenolic compound found in grapes and other fruits, is thought to contribute to the cardioprotective effect of red wine. While resveratrol exhibits some antiplatelet effect in vitro, the concentrations needed are much higher than those in plasma after consumption of red wine. In the present study, we investigate if resveratrol is able to potentiate the effect of endogenous antiplatelet substances--prostaglandin (PG) I2 and PGE1. In human platelet suspension resveratrol at relatively low concentrations (2 or 5 microM), which did not affect platelet function, significantly enhanced the inhibitory activity of PGs on platelet aggregation caused by collagen. The mechanisms underlying this effect may be associated with the inhibition of protein kinase C activation and protein tyrosine phosphorylation, but not with cyclic nucleotide levels and intracellular calcium mobilization in platelets. Our results might provide a possible explanation for the in vivo antiplatelet effect of resveratrol despite the poor bioavailability and the weak in vitro activity.

[Medical treatment of critical leg ischemia: current status and future perspectives of gene and cell therapy]. / Ischémie critique des membres inférieurs: traitement médical actuel et perspectives de la thérapie génique et cellulaire.

Critical limb ischemia (CLI) is associated with a high risk of amputation and death. For patients who cannot be surgically revascularized, medical options include prostanoids, spinal cord stimulation and lumbar sympathectomy, but none of these treatments has a demonstrated impact on the amputation rate at six months. Gene and cell therapy, aimed at stimulating angiogenesis, have mainly been tested in phase I and II clinical trials. These approaches appear to be feasible and safe in the short-term, but large randomized studies are necessary to demonstrate their clinical benefits and long-term safety.

Induction of labour at the start of the new millennium.

Around 20% of all deliveries are preceded by labour induction, a proportion that has not varied dramatically over recent years. Fetal death was the only indication for labour induction centuries ago, while this is now a very rare indication, with prolonged pregnancy and maternal hypertensive disorders being the major indications for the last 50-60 years. Techniques for inducing labour have also changed from dietary delicacies and verbal threats giving way to physical stimulation mainly achieved by cervical stretching and amniotomy and more recently to sophisticated pharmacological manipulation using oxytocin and prostaglandins, based on our expanding knowledge of the physiological processes involved in spontaneous parturition. Relaxin, antiprogestins, nitric oxide as well as complementary medicines have also been explored in recent years. Successful induction is, however, still not guaranteed and there has been increasing emphasis during the past decade on exploring strategies for identifying the probability of success. Measurement of fetal fibronectin in cervical mucus, maternal serum nitrite/nitrate concentrations, ultrasound delineation of cervical form and electrical impedance measurements across the cervix are all being investigated. Safety, success, and patient satisfaction continue to be the major objectives with economic evaluations now becoming a significant factor in the search for the ideal induction method.

Los endocanabinoides y el sueño / Endocannabinoids and sleep

La modulación del sueño depende de la participación de un dilatado numero de moléculas de diversa índole bioquímica. Dentro de las que más recientemente se han descrito están los lípidos. Estas moléculas que forman alrededor del 50 por ciento del peso del cerebro, y que la fisiología clásica no les ha adjudicado otro valor mas allá del de ser componentes estructurales de las membranas, participan en la transmisión de las señales neurofisiológicas. La importancia de estas moléculas en la neurotrasmisión ha venido a consolidarse con la descripción de una familia de ellas que tiene actividad de canabinoides. Dentro de ellas esta la anandamida, la oleamida y el 2-Araquidonilglicerol. Considerando que uno de los efectos que los canabinoides de origen vegetal producen es somnolencia, ha sido tarea de nuestro grupo describir, por primera vez en la ciencia, la función que los endocanabinoides cumplen en la regulación del sueño. En esta revisión discutimos los antecedentes y los hallazgos más recientes al respecto de este tema: Los endocanabinoides y el sueño (AU)

Neurotrophic actions of novel compounds designed from cyclopentenone prostaglandins.

Previously we found that some cyclopentenone prostaglandin derivatives promoted neurite outgrowth from PC12 cells and dorsal root ganglia explants in the presence of nerve growth factor; and so we referred to them as neurite outgrowth-promoting prostaglandins (NEPPs). In this study, NEPPs protected HT22 cells against oxidative glutamate toxicity. NEPP6, one of the most effective promoters of neurite outgrowth in PC12 cells, protected the cells most potently among NEPPs 1--10. Several derivatives, NEPPs 11--19, were newly synthesized based on the chemical structure of NEPP6. NEPP11 had a more potent neuroprotective effect than NEPP6. NEPP11 also prevented the death of cortical neurons induced by various stimuli and reduced ischemic brain damage in mice. Biotinylated compounds of NEPPs were synthesized to investigate their cellular accumulation. NEPP6-biotin protected the cells and emitted potent signals from the cells. In contrast, biotinylated non-neuroprotective derivatives emitted much weaker signals. These results suggest that NEPPs are novel types of neurotrophic compounds characterized by their dual biological activities of promoting neurite outgrowth and preventing neuronal death and that their accumulation in the cells is closely associated with their neuroprotective actions.

[Reconstructive and non-reconstructive procedures in the treatment of the threatened limb]. / Procedure ricostruttive e non ricostruttive nel trattamento dell'arto critico.

Limb threatening ischemia is an acute step in the chronic course of peripheral arterial obstructive disease that requires some form of intervention. The objective of this study is to prove that reconstructive surgery as well as non reconstructive approaches are associated with positive results. Ours is a retrospective analysis of a ten year experience in the treatment of limb threatening ischemia. In the period 1983-93, 139 patients under-went 164 procedures. 67% of patients were diabetics. Early in the observation period the therapeutic strategy was non reconstructive, the procedure of choice was sympathectomy. Later vascular reconstructions have been recognized as the procedures of choice. In the cases not amenable to reconstructive procedures according to our group criteria (absence of a tibial vessel in continuity with a patent pedal arch), we have employed procedures such as prostanoid infusion; thrombolysis and epidural spinal cord stimulation. Reconstructive procedures have been associated with a decrease in the number of major amputations. Alternative procedures, employed in patients not amenable to reconstruction have proven worthwhile in terms of limb salvage even if this trend is limited to a short period of observation.

Use of prostaglandins in nurse-midwifery practice.

Prostaglandin E2 (PGE2) is known to induce structural changes in the uterine cervix that produce thinning, softening, and eventually dilatation. In this paper, three certified nurse-midwives share their clinical experiences in using prostaglandin gel as a stimulus for labor.

Clinical aerosols II. Therapeutic aerosols.

The current uses of clinical aerosols such as water, saline, mucolytics, bronchodilators, cromolyn sodium, corticosteroids, and antimicrobials have been reviewed. The benefits of water, saline, and detergent aerosols continue to be surrounded by uncertainty and controversy. Aerosolized mucolytic and proteolytic agents have not been conclusively shown to be of substantial value in the improvement of respiratory disorders. Favorable bronchodilator therapy is achieved with aerosols of certain sympathomimetic and anticholinergic agents. However, successful therapy depends on the dose administered and the site of aerosol deposition in the lung. The prophylactic use of cromolyn sodium in patients with asthma is another useful application of aerosols. Topically active corticosteroid aerosols are increasingly being used since they may reduce risks of systemic effects from corticosteroids. Research on uncommonly aerosolized agents has widened the spectrum of therapeutic applications of aerosols.

The central nervous effect of prostaglandins I2, E2 and F2 alpha on aconitine-induced cardiac arrhythmia in rats.

Intracerebroventricular administration of PGI2 or PGE2 reduced aconitine-induced cardiac arrhythmia in rats. PGF2 alpha had no antiarrhythmic effect under the same conditions. The ED50 values of PGI2 and E2 were 0.25 microgram/kg and 1.1 microgram/kg, respectively. Central mechanisms may participate in the antiarrhythmic effect of these PGs.

Analogs of endoperoxide precursors of prostaglandins: failure to affect body temperature when injected into primary and secondary central temperature controls.

It is known that central administration of prostaglandins of the E series has marked effects on body temperature. The purpose in the present experiments was to learn whether stable analogs of the cyclic endoperoxide precursors of PGE2, PGF2alpha and PGD2, injected into the primary temperature control in the preoptic/anterior (PO/AH) hypothalamic region and into a presumed secondary control in the medulla oblongata, can produce rises in body temperature similar to those caused by PGE2. Injection of the analogs U-44069 and U-46619 (1.0 and 2.0 microng) into the PO/AH region of the rat, where both PGE2 and PGE1 caused hyperthermia, had no effect on Tre. Likewise, injections into the medulla oblongata, in the region where PGE2 and PGE1 caused hypothermia, were ineffective in altering body temperature. That neurons important to the control of body temperature are selectively sensitive to PGE2 and not to analogs of prostaglandin precursors suggests that local cyclic endoperoxides can influence body temperature only through bioconversion to prostaglandin.