Management of benign prostate hyperplasia (BPH) by combinatorial approach using alpha-1-adrenergic antagonists and 5-alpha-reductase inhibitors.

Currently, the main available treatments for benign prostate hyperplasia (BPH) are alpha-1 adrenergic receptor antagonists (ARAs), 5-alpha reductase inhibitors (5-αRI), anticholinergics, and Phosphodiesterase-5 inhibitors. Recent studies support the combined therapy approach using ARAs with 5-αRI for lower urinary tract symptoms (LUTS) in BPH patients at risk of clinical progression. We aimed to review BPH management in select group of randomized controlled trials by combination therapy with ARAs and 5-αRIs compared to monotherapy with either drug with respect to the safety and efficacy. A total of 6 randomized controlled trials (RCTs) involving comparison of combination therapy with monotherapy using ARAs and 5-αRIs were retrieved from PubMed Central and reviewed for international prostate symptom score (IPSS), quality of life (QoL), post-residual urinary flow rate (PUF), and clinical progression. The results significantly favour the treatment group that received the combination therapy in comparison with the groups receiving monotherapy. However, outcome with regard to prostate volume showed insignificant improvement when the combination therapy is compared with 5- αRIs alone, rather than ARAs. In conclusion, combination therapy using ARAs and 5-αRI is better than monotherapy in the patients of BPH. Fixed dose combination (FDC), a type of combination, is also cost-effective and its sideeffects profile resembles to that of monotherapy

REIMAGINING FUTURE RELATIONS BETWEEN INTERNATIONAL AND NATIONAL LAW WITH SPECIAL REFERENCE TO THE PALESTINIAN SITUATION

This paper examines the issue of the relationship between international and national law that leads to the gradation of laws. Is international law superior or inferior to national law? This question pushed the existing theoretical positions to find more convincing answers and practical solutions to this question. The article differentiates between two doctrines, the first is monism between international and national law, and the second is the dualism between international and national law. The status of international law in the national legal system is determined by the national constitution of each country. The article discusses a crucial issue associated with a substantial principle on which international law is based: the principle of state sovereignty and the critical relationship between international law and national law. The article aims to clarify the nature of the relationship with a specific reference to the experiences and challenges faced by the State of Palestine. To achieve the objectives of the article, doctrinal legal research methodology was adopted. Accordingly, this study concluded that there are two conflicting doctrines in determining the status of international law in the national legal system. Since the establishment of the State of Palestine and being a non-member observer state at the United Nations, the Palestinian legislature has adopted the doctrine of monism. The study would assist the international community in understanding the legal nature of the Palestinian constitutional system and its position related to the value of treaties in Palestine. The study emphasises the need to harmonise Palestinian legislation in order to be in line with international treaties

Heat Stroke in Emergency Department: Diagnosis and Management

Background: Heat stroke is a severe health concern with the potential for multi-organ failure, necessitating rapid and effective management. With rising global temperatures, there is increasing concern regarding the vulnerability of populations in high-heat areas, notably in Saudi Arabia, especially during the annual Hajj pilgrimage. Objective: This paper aims to review the epidemiology, evaluation and management techniques of heat stroke, emphasizing the situation during Hajj pilgrimages in Saudi Arabia, and to outline the best practices for emergency management. Methodology: A comprehensive review of literature and studies related to heat stroke, both globally and specific to Saudi Arabia, was undertaken. An in-depth analysis of emergency management, including initial assessment, cooling methods, organ support, medication, and prevention strategies, was conducted. Results: Heat stroke remains a significant cause of emergency department visits, with specific groups, such as men and the elderly, being more susceptible. During the Hajj in 2016, 267 patients were diagnosed with heat-related illnesses, with heatstroke accounting for 29% of these cases. With the threat of global warming, studies indicate a potential tenfold increase in heat stroke risk with a 2°C rise in temperatures. Swift and comprehensive cooling is pivotal for recovery. Management emphasizes rapid recognition, assessment, and varied cooling methods, along with targeted treatments for organ dysfunctions. Prevention strategies play a vital role, given the higher efficacy and practicality over treating organ dysfunctions. Conclusion: Heat stroke is a pressing health challenge, particularly in high-risk environments like Saudi Arabia during the Hajj pilgrimage. While effective emergency management protocols exist, an emphasis on prevention is crucial. It is imperative to incorporate a comprehensive approach to address both the immediate threat and long-term risks of heat stroke, especially with the looming challenge of global warming

The Impact Of Oral Health Education And Preventive Measures On Dental Caries And Periodontal Diseases

Oral problems, including dental caries, periodontal diseases, and tooth loss, are significant global public health concerns. This is due to the fact that inadequate oral health has extensive impacts on general health and quality of life. In improving oral health, especially in developing countries, there are obstacles that need to be addressed. It is crucial to enhance public health programs worldwide by implementing efficient preventative measures against diseases and simultaneously boosting oral health. Frequently, collective actions are employed for the purpose of oral health education. These actions often involve delivering lectures utilizing various materials such as flipcharts, videos, PowerPoint presentations, as well as implementing other activities like supervised teeth brushing and topical fluoride application. This paper aimed to review the impact of oral health education and preventive measures on dental caries and periodontal diseases

Melatonin ameliorates serobiochemical alterations and restores the cardio-nephro diabetic vascular and cellular alterations in streptozotocin-induced diabetic rats

Melatonin possesses a wide range of pharmacological activities, including antidiabetic properties. Diabetes mellitus (DM) induces several physiopathological changes in body organs, which could be observed lately after systemic failure. In the current study, we aimed to investigate the serobiochemical changes and the histopathological picture in the diabetic heart and the kidney early before chronic complications and highlight the association between hyperglycemia, glomerular alterations, and cardiovascular changes. In addition, the role of melatonin in the treatment of cardio-nephro diabetic vascular and cellular adverse changes in streptozotocin-induced diabetic rats was also studied. A total of 40 mature Wistar albino rats were distributed into five groups; (1) control untreated rats, (2) diabetic mellitus untreated (DM) rats, in which DM was induced by the injection of streptozotocin (STZ), (3) control melatonin-treated (MLT), (4) melatonin-treated diabetic (DM + MLT) rats, in which melatonin was injected (10 mg/kg/day, i.p.) for 4 weeks, and (5) insulin-treated diabetic (DM + INS) rats. The serum biochemical analysis of diabetic STZ rats showed a significant (P < 0.05) increase in the concentrations of blood glucose, total oxidative capacity (TOC), CK-MB, endothelin-1, myoglobin, H-FABP, ALT, AST, urea, and creatinine as compared to control rats. In contrast, there was a significant (P < 0.05) decrease in serum concentration of insulin, total antioxidative capacity (TAC), total nitric oxide (TNO), and total protein level in DM rats vs. the control rats. Significant improvement in the serobiochemical parameters was noticed in both (DM + MLT) and (DM + INS) groups as compared with (DM) rats. The histological examination of the DM group revealed a disorder of myofibers, cardiomyocyte nuclei, and an increase in connective tissue deposits in between cardiac tissues. Severe congestion and dilation of blood capillaries between cardiac muscle fibers were also observed. The nephropathic changes in DM rats revealed various deteriorations in glomeruli and renal tubular cells of the same group. In addition, vascular alterations in the arcuate artery at the corticomedullary junction and interstitial congestion take place. Melatonin administration repaired all these histopathological alterations to near-control levels. The study concluded that melatonin could be an effective therapeutic molecule for restoring serobiochemical and tissue histopathological alterations during diabetes mellitus

Melatonin downregulates the increased hepatic alpha-fetoprotein expression and restores pancreatic beta cells in a streptozotocin-induced diabetic rat model: a clinical, biochemical, immunohistochemical, and descriptive histopathological study

BackgroundDiabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes.ObjectiveThis study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how β-cells of the pancreas in diabetic rats respond to MT administration.Materials and methodsForty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively.ResultsMT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the β-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic β-cells; its antioxidant effect also reduced hepatocyte injury.ConclusionCollectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic β-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes

Unveiling the therapeutic potential of exogenous β-hydroxybutyrate for chronic colitis in rats: novel insights on autophagy, apoptosis, and pyroptosis

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colorectal area that demonstrates a dramatically increasing incidence worldwide. This study provides novel insights into the capacity of the exogenous β-hydroxybutyrate and ketogenic diet (KD) consumption to alleviate dextran sodium sulfate (DSS)-induced UC in rats. Remarkably, both interventions attenuated disease activity and colon weight-to-length ratio, and improved macro and microstructures of the damaged colon. Importantly, both β-hydroxybutyrate and KD curbed the DSS-induced aberrant NLRP3 inflammasome activation as observed in mRNA and protein expression analysis. Additionally, inhibition of the NLRP3/NGSDMD-mediated pyroptosis was detected in response to both regimens. In parallel, these modalities attenuated caspase-1 and its associated consequences of IL-1β and IL-18 overproduction. They also mitigated apoptosis as indicated by the inactivation of caspase-3. The anti-inflammatory effects of BHB and KD were confirmed by the reported decline in the levels of inflammatory markers including MPO, NFκB, IL-6, and TNF-α. Moreover, these interventions exhibited antioxidative properties by reducing ROS production and improving antioxidative enzymes. Their effectiveness in mitigating UC was also evident in the renovation of normal intestinal epithelial barrier function, as shown by correcting the discrepancies in the levels of tight junction proteins ZO-1, OCLN, and CLDN5. Furthermore, their effects on the intestinal microbiota homeostasis were investigated. In terms of autophagy, exogenous β-hydroxybutyrate upregulated BECN-1 and downregulated p62, which may account for its superiority over KD in attenuating colonic damage. In conclusion, this study provides experimental evidence supporting the potential therapeutic use of β-hydroxybutyrate or β-hydroxybutyrate-boosting regimens in UC

Contribution of Chondroitin Sulfate A to the Binding of Complement Proteins to Activated Platelets

Exposure of chondroitin sulfate A (CS-A) on the surface of activated platelets is well established. The aim of the present study was to investigate to what extent CS-A contributes to the binding of the complement recognition molecule C1q and the complement regulators C1 inhibitor (C1INH), C4b-binding protein (C4BP), and factor H to platelets.Human blood serum was passed over Sepharose conjugated with CS-A, and CS-A-specific binding proteins were identified by Western blotting and mass spectrometric analysis. C1q was shown to be the main protein that specifically bound to CS-A, but C4BP and factor H were also shown to interact. Binding of C1INH was dependent of the presence of C1q and then not bound to CS-A from C1q-depleted serum. The specific interactions observed of these proteins with CS-A were subsequently confirmed by surface plasmon resonance analysis using purified proteins. Importantly, C1q, C4BP, and factor H were also shown to bind to activated platelets and this interaction was inhibited by a CS-A-specific monoclonal antibody, thereby linking the binding of C1q, C4BP, and factor H to exposure of CS-A on activated platelets. CS-A-bound C1q was also shown to amplify the binding of model immune complexes to both microtiter plate-bound CS-A and to activated platelets.This study supports the concept that CS-A contributes to the binding of C1q, C4BP, and factor H to platelets, thereby adding CS-A to the previously reported binding sites for these proteins on the platelet surface. CS-A-bound C1q also seems to amplify the binding of immune complexes to activated platelets, suggesting a role for this molecule in immune complex diseases

Sodium Stibogluconate (SSG) & Paromomycin Combination Compared to SSG for Visceral Leishmaniasis in East Africa: A Randomised Controlled Trial

Visceral leishmaniasis (VL) is a parasitic disease with about 500,000 new cases each year and is fatal if untreated. The current standard therapy involves long courses, has toxicity and there is evidence of increasing resistance. New and better treatment options are urgently needed. Recently, the antibiotic paromomycin (PM) was tested and registered in India to treat this disease, but the same dose of PM monotherapy evaluated and registered in India was not efficacious in Sudan. This article reports the results of a clinical trial to test the effectiveness of injectable PM either alone (in a higher dose) or in combination with sodium stibogluconate (SSG) against the standard SSG monotherapy treatment in four East African countries—Sudan, Kenya, Ethiopia and Uganda. The study showed that the combination of SSG &PM was as efficacious and safe as the standard SSG treatment, with the advantages of being cheaper and requiring only 17 days rather than 30 days of treatment. In March 2010, a WHO Expert Committee recommended the use of the SSG & PM combination as a first line treatment for VL in East Africa