Gastric effects of cholecystokinin and its interaction with leptin on brainstem neuronal activity in neonatal rats

Cholecystokinin (CCK) is a major gastrointestinal neuropeptide that is secreted in response to food ingestion. It is involved in the feedback regulation of gastric emptying and also modulates food intake. Leptin, a hormone that regulates food intake and energy balance, is secreted from adipose tissue, gastric mucosa, fundic glands, and other tissues. In a previous report we showed that gastric effects of leptin activated the nucleus tractus solitarius (NTS) neurons responding to gastric vagal stimulation. In this study, using the same in vitro neonatal rat preparation, we investigated the gastric effects of CCK and its interaction with leptin on NTS neurons receiving gastric vagal inputs. We observed that peripheral gastric effects of CCK (300 nM) produced a mean activation response of 271 +/- 3.9% compared with control level (100%) in 33 (60%) neurons tested (P <.01), and this response was abolished by a CCK-A receptor antagonist. A concentration-dependent effect of CCK (10 nM-1.0 microM) on NTS neuronal discharge frequencies was shown. We also observed that leptin (10 nM) applied to the stomach produced a mean activation response of 183 +/- 5.3% in 13 (50%) NTS units that responded to CCK (P <.01). Furthermore, we evaluated the combined effect of CCK and leptin in two groups of NTS neurons. Those NTS units that showed activation responses to both CCK (300 nM) and leptin (10 nM) had a subadditive effect that produced a mean activation response of 338 +/- 12.9% compared with the control level in all 10 (100%) neurons tested (P <.01). Eight (36%) of another 22 units that were not affected by either CCK (300 nM) or leptin (10 nM) alone had an activation response (151 +/- 5.2%; P <.05) when the same concentrations of CCK and leptin were applied together. Subsequently, by comparing the effects of CCK and leptin on a whole-stomach preparation to a partial-stomach preparation, we examined the area of the stomach in which gastric receptors contributed most to NTS unitary activity. We showed that the distal stomach containing the pylorus determined CCK gastric activity, whereas both the proximal and distal stomach are important for leptin's effect. Our data suggest that leptin modulates the potency of CCK signals that modify food intake in the neonatal rat.     

Evaluation and treatment of erectile dysfunction in men with diabetes mellitus

Diabetic men have a more than 3-fold increased prevalence of erectile dysfunction (ED) compared with nondiabetic men. Erectile function is primarily a vascular phenomenon, triggered by neurologic controls and facilitated by appropriate hormonal and psychological components. Recent advances in the understanding of the physiology of penile vasculature and its role in male sexual performance have influenced the clinical approach to ED. The pathophysiological alterations leading to impotence in diabetic men include vasculogenic, neurogenic, and hormonal etiologies. A clinical work-up, including a thorough history and physical examination, is an important aspect of ED management. Biochemical evaluations to rule out secondary causes like hypogonadism and thyroid abnormalities are suggested. Oral medications acting through phosphodiesterase inhibition in penile vasculature have revolutionized treatment of impotence in diabetic men. Because of a high success rate in treating ED of various etiologies, these agents are the treatment of choice for most patients. Safety and efficacy of vacuum-constriction devices, intraurethral suppositories, intracavernosal injections, and other therapies are discussed. A clinical algorithm for the evaluation and management of ED is provided for use in the primary care setting.     

Monitoring for undertransfusion

BACKGROUND: Most published reviews and audits of blood and blood component transfusion have focused on the issue of overtransfusion and on the inappropriate use of red cell components. There is growing concern that efforts to curb unnecessary transfusions may result in a trend toward undertransfusion of patients. There is little published information that addresses this issue or the magnitude of this practice. STUDY DESIGN AND METHODS: Undertransfusion was evaluated by examining the transfusion records from a 3-month period for 55 patients who met the study criteria of having either a hemoglobin level < 7 g per dL or a platelet count of < 10 × 10(9) per L. If the identified patient did not receive a transfusion within 24 hours of the reported hemoglobin level or platelet count, the medical record was reviewed by a resident physician. RESULTS: A total of 213 individual hemoglobin levels and platelet counts, representing the 55 patients, met our transfusion criteria. All except 8 of the identified patients received red cells and/or platelet transfusions. Reasons for not transfusing red cells included the patient's response to nutritional support and iron supplementation, refusal of blood, and noncompliance. Reasons for not transfusing platelets included falsely low platelet count because of platelet clumping in vitro, contraindication based on clinical diagnosis (e.g., immune thrombocytopenic purpura), and the patient's death before transfusion. CONCLUSION: Red cell and platelet transfusions were appropriately ordered for all patients who met the transfusion criteria. Undertransfusion is not a problem at this institution according to the criteria established. It is recommended that other institutions expand their blood utilization audits to include investigation for evidence of undertransfusion. Further research regarding the issue of undertransfusion is warranted and could be expanded to include other components.     

Oral sumatriptan in the acute treatment of migraine and migraine recurrence in general practice

We investigated the efficacy, safety and tolerability compared with placebo of a second dose of oral sumatriptan 100 mg in 1349 general practice patients who had already treated a moderate or severe migraine headache with 100 mg sumatriptan 4 h earlier. Headache was relieved by the first sumatriptan dose in about 70% of patients, but the second dose did not produce significantly more relief than placebo, either in nonresponders or in the group as a whole, nor did it reduce other symptoms (photophobia, nausea, vomiting, etc,) at 8 h, or influence the incidence of headache recurrence. The drug was well-tolerated, and a further single dose was effective in treating recurrence after initial relief. A single 100 mg dose of sumatriptan is an effective acute treatment for migraine. A second dose should be reserved for treating headache recurrence.      

Neue Operationsverfahren am Akromioklavikulargelenk und an der lateralen Klavikula

Background

Instabilities of the acromioclavicular joint and fractures of the lateral clavicle belong to the most common trauma sequelae of the shoulder girdle. A variety of surgical procedures have been described for these pathologies and a number of innovations were recently introduced. This article gives an overview about the current state of knowledge and useful tips for the daily clinical routine.

Methods

For both pathologies minimally invasive arthroscopically-assisted procedures are being used increasingly more. Compared to conventional open procedures several advantages are evident: less approach-related morbidity, the possibility of detection and treatment of common concomitant pathologies and a one-stage procedure without a mandatory implant removal.

Results

Very good mid-term results have been published for the arthroscopic double-button technique for treatment of acromioclavicular instability. For fracture treatment the appropriate procedure must be chosen depending on the individual fracture morphology. The hybrid procedure consisting of plate osteosynthesis and coracoclavicular augmentation is the most stable technique.

     

Effectiveness of a community-based water,sanitation, and hygiene (WASH) intervention in reduction of diarrhoea among under-five children: Evidence from a repeated cross-sectional study (2007–2015) in rural Bangladesh

Diarrhoea, the most common disease directly related to water, sanitation, and hygiene (WASH), still remains one of the most significant health problems among children under-five worldwide. In this reality, BRAC, the largest NGO in the world initiated a comprehensive WASH intervention in 50 upazilas (sub-districts) of Bangladesh in 2007 which was later scaled up to cover 150 upazilas in two subsequent phases. The intervention period of the programme was 2007–2011.The present study encompassed 30 upazilas of the first phase of intervention. The aim of the study was to investigate the effectiveness of this intervention on reduction of diarrhoea among under-five children, and to identify the factors associated with childhood diarrhoea. A repeated cross-sectional study design was followed, and a population-based survey was carried out on four occasions: baseline (2007), midline (2009), endline (2011), and post-endline (2015) among 4,775 households. This analysis considers only households having at least one under-five children.Absence of handwashing practice with soap after defecation and before eating food, unclean latrine condition, and unsafe disposal of child faeces were identified as significant risk factors associated with under-five diarrhoea from Log-binomial regression. The prevalence of under-five diarrhoea within the past 2 weeks of the survey declined from 13.7% at baseline to 3.6% at end-line (p < 0.001) in the WASH intervention area. However, the progress seemingly stalled after 2011, which may have occurred due to the lack of improvement in unsafe disposal of child faeces and unclean latrine condition after the intervention period.Study findings suggest that, to reduce the prevalence of childhood diarrhoea it is important to promote safe disposal of child faeces, maintaining cleanliness of latrines, and washing hand with soap at critical times, beyond merely increasing the sanitation coverage. Findings also underline the necessity of maintaining a small-scale monitoring component involving local community, such as a WatSan committee (a local committee comprising the user communities for supervising WASH related activities) for periodic monitoring at household level for a certain period after the program intervention works to make the behavioural change more sustainable and to keep the reduction rate of under-five diarrhoeal prevalence steady.     

Amino acid based amphiphilic copolymer micelles as carriers of non-steroidal anti-inflammatory drugs: solubilization, in vitro release and biological evaluation

Three novel amino acid based anionic amphiphilic copolymers poly(sodium N-acryloyl-l-valinate-co-alkylacrylamide) (where, alkyl=octyl and dodecyl) with either 9 or 16 mol% hydrophobic substitution were synthesized. These hydrophobically modified polyelectrolytes (HMPs), above a critical concentration, self-assemble in aqueous solution through inter-chain hydrophobic aggregation, forming micelle-like aggregates having hydrodynamic diameter in the range of 50-200 nm. The HMPs were found to undergo conformational changes with the change in solution pH, electrolyte and additive concentration, and temperature. The polymeric micelles were observed to be stable under biological conditions (pH 7.4, [NaCl]=150 mM and temperature (37°C)). The solubilization capacity of the polymeric micelles for six important non-steroidal anti-inflammatory drugs of different hydrophobicity was evaluated. Depending upon the hydrophobicity the solubilities of the drugs were observed to increase ca. 2-10 times in the presence of 1.0 g/L copolymers. The in vitro release kinetics of the loaded drug was studied under physiological pH. To explore their potential application in pharmaceutical industries hemocompatibility and cytotoxicity studies were carried out using hemolytic and MTT assay, respectively. The anionic HMPs were found to be not directly toxic to mammalian cells.