Berberine for prevention of dementia associated with diabetes and its comorbidities: A systematic review.

BACKGROUND: A growing number of epidemiological studies indicate that metabolic syndrome (MetS) and its associated features play a key role in the development of certain degenerative brain disorders, including Alzheimer's disease and vascular dementia. Produced by several different medicinal plants, berberine is a bioactive alkaloid with a wide range of pharmacological effects, including antidiabetic effects. However, it is not clear whether berberine could prevent the development of dementia in association with diabetes. OBJECTIVE: To give an overview of the therapeutic potential of berberine as a treatment for dementia associated with diabetes. SEARCH STRATEGY: Database searches A and B were conducted using PubMed and ScienceDirect. In search A, studies on berberine's antidementia activities were identified using "berberine" and "dementia" as search terms. In search B, recent studies on berberine's effects on diabetes were surveyed using "berberine" and "diabetes" as search terms. INCLUSION CRITERIA: Clinical and preclinical studies that investigated berberine's effects associated with MetS and cognitive dysfunction were included. DATA EXTRACTION AND ANALYSIS: Data from studies were extracted by one author, and checked by a second; quality assessments were performed independently by two authors. RESULTS: In search A, 61 articles were identified, and 22 original research articles were selected. In search B, 458 articles were identified, of which 101 were deemed relevant and selected. Three duplicates were removed, and a total of 120 articles were reviewed for this study. The results demonstrate that berberine exerts beneficial effects directly in the brain: enhancing cholinergic neurotransmission, improving cerebral blood flow, protecting neurons from inflammation, limiting hyperphosphorylation of tau and facilitating ß-amyloid peptide clearance. In addition, evidence is growing that berberine is effective against diabetes and associated disorders, such as atherosclerosis, cardiomyopathy, hypertension, hepatic steatosis, diabetic nephropathy, gut dysbiosis, retinopathy and neuropathy, suggesting indirect benefits for the prevention of dementia. CONCLUSION: Berberine could impede the development of dementia via multiple mechanisms: preventing brain damages and enhancing cognition directly in the brain, and indirectly through alleviating risk factors such as metabolic dysfunction, and cardiovascular, kidney and liver diseases. This study provided evidence to support the value of berberine in the prevention of dementia associated with MetS.

Repetitive administration of acetylcholine receptor agonist rescues brain inflammation and brain damage after hypoxia-ischemia in newborn rat.

OBJECTIVE: We examined the effect of repetitive administration of acetylcholine receptor agonist (carbachol) on brain damage and microglial accumulation in three brain regions after hypoxia-ischemia (HI) in newborn rat. STUDY DESIGN: Seven-day-old Wistar rats were divided into two groups, one receiving a 0.1 mg/kg dose of carbachol on days 7, 8 and 9 to examine the attenuating effect on brain damage with decreasing accumulation of microglia, and the other group receiving saline as a control. Rats were subjected to left carotid artery ligation followed by hypoxia. We evaluated brain damage and the number of microglias in three regions on days 10 and 14. RESULTS: Brain tissue was better preserved in the carbachol group on days 10 and 14. Microglial accumulation in the cortex was strong and persisted from day 10s to 14 in the control. Conversely, the accumulation of microglias was attenuated in the hippocampus and white matter on day 14. Carbachol significantly reduced the number of microglias in the hippocampus and white matter on day 10 and in the cortex on days 10 and 14. CONCLUSION: The main area of late inflammation was the cortex. Repetitive administration of carbachol reduces early and late inflammation after HI in the developing brain.

Tratamento da síndrome da bexiga hiperativa idiopática refratária / Treatment of idiopathic refractory overactive bladder syndrome

A síndrome da bexiga hiperativa é um distúrbio caracterizado pela presença de urgência miccional, podendo ou não haver incontinência urinária associada. Afeta homens e mulheres em iguais proporções, mas tem maior impacto sobre a população feminina, já que a incidência de incontinência é maior. O tratamento de primeira linha consiste em medidas comportamentais, treinamento vesical e fisioterapia, podendo-se associar tratamento farmacológico em casos persistentes. As drogas mais frequentemente utilizadas são os anticolinérgicos, medicações eficazes, porém associadas a efeitos adversos incômodos que frequentemente limitam a aderência. Uma proporção considerável de mulheres não obtém êxito com a combinação de medidas conservadoras e medicações anticolinérgicas, seja por eficácia limitada, seja por efeitos colaterais intoleráveis. Para essa população, modalidades de tratamento de segunda e terceira linha podem trazer alívio sintomático e melhora da qualidade de vida. Além disso, foi recentemente aprovada uma nova classe de drogas para o tratamento da bexiga hiperativa, os agonistas de receptores ?3-adrenérgicos, que prometem eficácia equivalente aos anticolinérgicos sem os efeitos adversos que os limitam...

Overactive bladder syndrome is a condition characterized by urgency, with or without urinary incontinence. It affects men and women equally, but has a greater impact on the female population, given the higher prevalence of urgency-incontinence. First line treatment consists on lifestyle interventions, bladder drills and physical therapy. Pharmacological treatment may be associated in persistent cases. The most commonly used medications are anticholinergics, which are efficacious, but limited by a variety of bothersome adverse effects that impair treatment compliance. A significant proportion of women don?t experience a successful outcome with the combination of conservative measures and treatment with anticholinergics, owing both to limited efficacy and to intolerable adverse effects that lead to treatment discontinuation. For this population, second and third line therapies may provide symptomatic relief, with great improvement in health related quality of life. Also, a new class of drugs, the ?3-adrenergic receptor agonists, has recently been approved for the treatment of overactive bladder, and may provide similar efficacy to currently used anticholinergic drugs without the associated adverse effects...

Applied clinical pharmacology and public health in rural Asia--preventing deaths from organophosphorus pesticide and yellow oleander poisoning.

Self-poisoning with pesticides or plants is a major clinical problem in rural Asia, killing several hundred thousand people every year. Over the last 17 years, our clinical toxicology and pharmacology group has carried out clinical studies in the North Central Province of Sri Lanka to improve treatment and reduce deaths. Studies have looked at the effectiveness of anti-digoxin Fab in cardiac glycoside plant poisoning, multiple dose activated charcoal in all poisoning, and pralidoxime in moderate toxicity organophosphorus insecticide poisoning. More recently, using a Haddon matrix as a guide, we have started conducting public health and animal studies to find strategies that may work outside of the hospital. Based on the 2009 GSK Research in Clinical Pharmacology prize lecture, this review shows the evolution of the group's research from a clinical pharmacology approach to one that studies possible interventions at multiple levels, including the patient, the community and government legislation.

Soybean supplementation helps reverse age- and scopolamine-induced memory deficits in mice.

Phytoestrogens are nonsteroidal plant compounds that are able to exert estrogenic effects. Soybean is a rich source of phytoestrogens, especially isoflavones. Soy isoflavones are utilized for estrogen replacement therapy. Estrogen is reported to influence several areas of brain that are involved in cognition and behavior. Therefore, the present study was undertaken to examine whether dietary supplementation with soybean improves the cognitive function of mice. Soybean was administered in three different concentrations (2%, 5% and 10% [wt/wt]) in the normal diet to young and mature mice for 60 successive days. The passive avoidance paradigm and the elevated plus maze served as the exteroceptive behavioral models, whereas scopolamine (1.4 mg/kg, i.p.) served as the interoceptive behavioral model. The brain acetylcholinesterase activity (AChE) activity, brain thiobarbituric acid-reactive substances (TBARS), reduced glutathione (GSH), and total blood cholesterol levels were also measured in the present study. The administration of soybean for 60 consecutive days protected (P < .05) the animals from developing memory impairment. Soybean administration also resulted in diminished brain AChE activity, decrease in brain TBARS, and increase in GSH levels, thereby indicating facilitated cholinergic transmission, reduced free radical generation, and enhanced scavenging of free radicals. Thus, soybean appears to be a useful remedy for improving memory and for the management of cognitive deficits owing to its pro-estrogenic, antioxidant, procholinergic, and/or neuroprotective properties.

Cognitive function as an emerging treatment target for marijuana addiction.

Cannabis is the most widely used illicit substance in the world, and demand for effective treatment is increasing. However, abstinence rates following behavioral therapies have been modest, and there are no effective pharmacotherapies for the treatment of cannabis addiction. We propose a novel research agenda and a potential treatment strategy, based on observations that both acute and chronic exposure to cannabis are associated with dose-related cognitive impairments, most consistently in attention, working memory, verbal learning, and memory functions. These impairments are not completely reversible upon cessation of marijuana use, and moreover may interfere with the treatment of marijuana addiction. Therefore, targeting cognitive impairment associated with chronic marijuana use may be a promising novel strategy for the treatment of marijuana addiction. Preclinical studies suggest that medications enhancing the cholinergic transmission may attenuate cannabis-induced cognitive impairments, but these cognitive enhancing medications have not been examined in controlled human studies. Preliminary evidence from individuals addicted to other drugs suggests that computerized cognitive rehabilitation may also have utility to improve cognitive function in marijuana users. Future clinical studies optimally designed to measure cognitive function as well as drug use behavior would be needed to test the efficacy of these treatments for marijuana addiction.

Comparative efficacy of pilocarpine, timolol and latanoprost in experimental models of glaucoma.

Intraocular pressure (IOP)-lowering effects of investigational antiglaucoma drugs often need comparison with existing drugs, but detailed data showing comparative efficacy of antiglaucoma drugs with different mechanism of action has not been reported so far. This study was designed to establish baseline information of the IOP-lowering effect of three currently used antiglaucoma drugs in three experimental models in rabbits, so that they act as a benchmark for the efficacy evaluation of the future experimental antiglaucoma drugs. The IOP-lowering effect of single-drop application of pilocarpine, timolol and latanoprost was studied in normotensive, water loading and steroid-induced models of glaucoma in rabbits. The noncontact tonometer was used for the first time to estimate IOP in rabbits. The peak IOP-lowering effect of pilocarpine, timolol and latanoprost in normotensive rabbit eye was 18.23%, 20% and 22.56%, respectively. In water-loading model, the maximum protection against the rise in IOP was shown by latanoprost (40.27%), followed by timolol (31.39%) and pilocarpine (28.91%). In steroid-pretreated rabbit eyes, peak IOP-lowering effects of pilocarpine, timolol and latanoprost were 25.65%, 34.21% and 35.06%, respectively. Therefore, the latanoprost was found to be most effective in all three models followed by timolol and pilocarpine. The results of this study can be used for future preclinical investigations for the assessment of IOP-lowering activity of potential antiglaucoma drugs.

Pharmacological advancements in the treatment of chronic anal fissure.

Chronic anal fissure is a tear in the lining of the anal canal that, if not treated appropriately at an early stage, causes considerable anal pain during defaecation. Surgery is no longer considered the first-line treatment of this common condition, as recent advancements in medical treatment has produced promising results in the healing of fissures, thus avoiding the unwanted complications that frequently occur following operative treatment. This review looks at those pharmacological agents used commonly in the treatment of chronic anal fissures and explores alternative therapies that may be of benefit in the future.

Pathophysiology and management of radiation-induced xerostomia.

Radiotherapeutic treatment of head and neck cancer patients often causes long-term dysfunction involving their salivary function, swallowing capabilities, and taste. Salivary gland dysfunction from radiation therapy is often the most unpleasant side effect of treatment. This article will review current knowledge concerning the anatomy and function of glands involved with salivation, measurement of salivary gland function, surgical and pharmacologic prevention and treatment of xerostomia, and methods to administer radiation while causing the least amount of damage to salivary glands.

[Treatment of Alzheimer's disease]. / tratamiento de la enfermedad de Alzheimer.

OBJECTIVE: To review the experience of the last twenty years in the treatment of Alzheimer s disease (AD). METHODS: Literature review. RESULTS: The neuropathological bases of AD are centered on two important pathophysiological mechanisms: 1) Structural damage (e.g., senile plaques, neurofibrillary tangles, neuronal loss, inflammatory processes), and 2) Loss of cholinergic neurons (and acetylcholine depletion) in the nucleus basalis of Meynert, which sends cholinergic projections to all areas of the neocortex, especially the temporal lobes and frontal and parietal association areas. The indemnity of this system is essential for normal cognitive functioning. At this moment, the only long term treatment available for AD are acetylcholinesterase inhibitors (CEIs) (e.g., tacrine, donepezil, rivastigmine, galanthamine). There are being investigated several treatments that may alter the development of neurofibrillary tangles and neuritic plaques (e.g., peripherally administered antibodies against beta amyloid proteins). Nerve growth factors may have the capability of improving neuronal survival, although their form of administration remains a problem. Amelioration of oxidative stress and CNS inflammatory processes may slow dawn the rate of neurodegeneration. CONCLUSION: All suspected mechanisms of the metabolic cascade of AD have been explored with specific and non specific treatments. Current treatments (e.g., CEIs) still have to prove that their effects can last for long periods of time. With the advent of further understanding of the neurodegenerative processes that cause AD, new treatments that may slow down the progression of the disease will be available.

Salivary gland dysfunction: a review of systemic therapies.

Xerostomia may result from salivary dysfunction secondary to a variety of conditions, including medications, autoimmune disease, and tumoricidal therapy. As the geriatric population increases, the incidence of xerostomia will increase and the oral manifestations will continue to be a challenge to the clinician. Common oral manifestations resulting from decreased salivary flow include increased dental caries, fungal infections, and dysphagia. Treatment for salivary gland dysfunction is currently limited because of a lack of controlled clinical trials. Medications that have been studied in clinical trials are emphasized in this article. The aim of this article is to briefly review salivary gland physiology and to summarize the suggested systemic treatment modalities for xerostomia that emphasize controlled clinical trials.

Effects of chewing betel nut (Areca catechu) on the symptoms of people with schizophrenia in Palau, Micronesia.

BACKGROUND: Although millions of people with schizophrenia live in betel chewing regions, the effects of betel chewing on their symptoms are unknown. Betel nut alkaloids include potent muscarinic cholinomimetics: recent research suggests that these agents may be therapeutic in schizophrenia. AIMS: To compare the primary and extrapyramidal symptom profiles and substance-using habits of betel chewing v. non-chewing people with schizophrenia. METHOD: A cross-sectional study of 70 people with schizophrenia. Symptom ratings measured by the Positive and Negative Syndrome Scale (PANSS) and Extrapyramidal Symptom Rating Scale (ESRS), and demographic and substance-use data, were compared for 40 chewers and 30 non-chewers of betel nut. RESULTS: Betel chewers with schizophrenia scored significantly lower on the positive (P = 0.001) and negative (P = 0.002) sub-scales of the PANSS than did non-chewers. There were no significant differences in extrapyramidal symptoms or tardive dyskinesia. CONCLUSIONS: Betel chewing is associated with milder symptomatology and avoidance of more harmful recreational drugs. These initial results indicate that longitudinal research is merited.