Ghrelin and growth hormone secretagogues (GHS): modulation of growth hormone secretion and therapeutic applications

Growth hormone-releasing hormone (GHRH) and somatostatin modulate growth hormone (GH) secretion. A third mechanism was discovered in the last decade, involving the action of growth hormone secretagogues (GHS). Ghrelin, the endogenous ligand of the GHS-receptor, is an acylated peptide mainly produced by the stomach, but also synthesized in the hypothalamus. This compound increases both GH release and food intake. Endogenous ghrelin might amplify the basic pattern of GH secretion, optimizing somatotroph responsiveness to GHRH, activating multiple interdependent intracellular pathways. However, its main site of action is the hypothalamus. In the current paper it is reviewed the available data on the discovery of this peptide, the mechanisms of action and possible physiological roles of the GHS and ghrelin on GH secretion, and finally, the possible therapeutic applications of these compounds.     

Chronic constipation - the role of clinical assessment and colorectal physiologic tests to obtain an etiologic diagnosis

BACKGROUND: Diagnosis of subtypes of chronic constipation has been considered difficult to achieve even in specialized centers. Although colorectal physiologic tests have brought an important contribution, it remains unclear in which patients these tests should be indicated for. AIMS: This study aims to establish a differential diagnosis for chronic constipation cases using clinical assessment and physiologic tests and to identify clinical parameters that could predict which patients need physiologic tests. METHODS: One hundred and seventy nine patients (83% females; mean age, 45) with chronic constipation according to Rome II criteria were initially treated by dietary advice and functional reeducation and those unresponsive (110 or 61.5%) were submitted to colonic transit time, defecography, anorectal manometry and electromyography, as needed. RESULTS: A differential diagnosis was achieved in 63.6% of patients tested. However, 61.5% of 179 patients with chronic constipation (69 with no need to tests and 40 with normal tests) have etiologic diagnosis established only on clinical basis. Irritable bowel syndrome (32%), pelvic floor dysfunction (29%) and functional constipation due to faulty diet and life style habits (22%) were the main causes of chronic constipation. Alternating constipation and nausea/vomiting were symptoms significantly related to the diagnosis of irritable bowel syndrome; younger age, larger intervals between bowel movements, occurrence of fecal impaction and necessity of enema were related to the diagnosis of non-chagasic megacolon and digital assistance to evacuate and large rectocele or spastic pelvic floor on rectal exam were associated to pelvic floor dysfunction. Patients with long-standing constipation, fecal impaction, abdominal pain not eased after defecation, necessity for enemas, digital assistance and evidence of rectocele tended to be in need for physiologic tests to define the cause of chronic constipation. CONCLUSIONS: The etiologic diagnosis of chronic constipation can be achieved in most of patients on a clinical basis and some symptoms may be significantly related to specific diagnoses. Indications for physiologic tests should be based on specific clinical parameters.     

Optimal Timing of Implantable Cardioverter‐Defibrillator Implantation After Myocardial Infarction: A Decision Analysis

ICD Implant Timing . Background: The optimal timing of implantable cardioverter defibrillator (ICD) placement for the primary prevention of sudden cardiac death after myocardial infarction (MI) remains unknown. Methods and Results: We developed a Markov model to investigate the optimal timing of ICD implantation after MI (no ICD, ICD at 60 days, 6 months, and 1 year) in patients who meet current guidelines. Estimates of arrhythmic death (baseline risk 6%, range 1–20% per year), nonarrhythmic death, and ICD efficacy were based upon MADIT‐II and other contemporary post‐MI clinical trials. We used both deterministic and stochastic modeling processes in our analysis. After 10 years follow‐up, the baseline probability of survival was higher in those treated with ICD implantation versus not (42% vs 30%, P < 0.001). Survival was highest with ICD implantation at 60 days versus 6 months versus 1 year: 42.4%, 42.3%, and 42.0% (P = 0.0028). ICD implantation at 60 days provided a mean incremental survival of 0.28 months and 0.84 months per patient (compared with implantation at 6 months and 1 year). In sensitivity analyses, patients’ competing risk for nonarrhythmic death was the primary determinant of benefit from ICD implantation. Overall, ICD implantation at 60 days resulted in the greatest life expectancy over a wide range of plausible nonarrhythmic and arrhythmic death rates. Conclusions: The benefits of early ICD implantation are modest when compared with delayed implantation at 6 months/1 year. Our results suggest that making sure a patient receives an ICD, when appropriate, may be more important than the timing of the implantation procedure. (J Cardiovasc Electrophysiol, Vol. pp. 791‐798, July 2010)     

Creatine supplementation for patients with COPD receiving pulmonary rehabilitation: A systematic review and meta‐analysis

Background and objective: Creatine improves muscle strength in exercising healthy individuals, and in patients with neuromuscular disease and heart failure. The aim of this study was to assess whether creatine supplementation improves pulmonary rehabilitation (PR) outcomes in patients with COPD. Methods: A systematic review and meta‐analysis was performed of randomized controlled trials published between January 1966 and February 2009 that evaluated the effect of creatine compared with placebo on exercise capacity, muscle strength and health‐related quality of life (HR‐QoL) in patients undergoing PR for COPD. The pooled estimates were expressed as mean differences (MD) or standardized mean differences (SMD). Results: Four randomized controlled trials that included 151 patients were identified. There was no effect of creatine supplementation on exercise capacity (SMD ?0.01, 95% CI: ?0.42 to 0.22, n = 151). Creatine supplementation did not improve lower extremity muscle strength (SMD 0.03, 95% CI: ?0.55 to 0.61, n = 140) or upper limb muscular strength (SMD 0.02, 95% CI: ?0.33 to 0.38, n = 128) compared with placebo. Two studies (n = 48) assessed quality of life using the St. George's Respiratory Disease Questionnaire. There were no differences in HR‐QoL according to domain or total scores. Overall, creatine appeared to be safe and was well tolerated. Quality assessment of the studies showed important limitations. Conclusions: Creatine supplementation does not improve exercise capacity, muscle strength or HR‐QoL in patients with COPD receiving PR. However, important limitations were identified in the quality of the available evidence, suggesting that further research is required in this area.     

The occurrence of arthropods in processed rice products in Malaysia

ObjectiveTo determine distribution of arthropods in processed rice products such as rice flour and rice cereal-based infant food.MethodsRandom samples of rice flour and rice cereal-based infant food purchased from commercial outlets were examined for the presence of arthropods using a modified Berlese Tullgren Funnel Method. Mites were mounted prior to identification and weevils were directly identified.ResultsFor non-expired products, infestation was found in 6.7% of rice flour and none was found in rice cereal-based infant food samples. The arthropods found in the flour samples were Cheyletus spp., Suidasia pontifica (S. pontifica), Tarsonemus spp., Tyrophagus putrescentiae (T. putrescentiae), Sitophilus granarius (S. granarius) and Sitophilus oryzae (S. oryzae). Others which cannot be identified were Oribatid and Prostigmatid mites. The most common mites in rice flour were Tarsonemus spp. (69.1%), followed by S. pontifica (18.2%). For expired products, only one sample of rice cereal-based infant food was infested and the infestation was by mites of the family Tydeidae.ConclusionsThis study demonstrates the presence of 4 allergenic species of S. pontifica, T. putrescentiae, S. granarius and S. oryzae in rice flour. These arthropods can contribute to the incidence of anaphylaxis upon consumption by atopic individuals. There was no infestation of arthropods in rice cereal-based infant food surveyed except for an expired product in a moderate rusty tin container.     

Resistance to the organophosphate temephos: Mechanisms, evolution and reversion in an Aedes aegypti laboratory strain from Brazil

Insecticide resistance is one of the main problems in vector control programs. Because insects have developed resistance to all classes of available chemical insecticides, a proper surveillance and management of resistance in areas where these compounds are being utilized is crucial for the success of control programs. Since the mechanisms and molecular bases of resistance are various, they must be characterized to allow efficient monitoring strategies. Here we report the establishment of an Aedes aegypti strain resistant to temephos, named RecR, selected under laboratory conditions. The parental A. aegypti population was obtained from eggs collected in an area where temephos had been used for 8 years, and presented a baseline resistance ratio (RR) of 7. After 17 generations under selective pressure, the RR has increased to 180. Biochemical assays indicate that metabolic mechanisms are involved on temephos resistance in the selected strain. These experiments showed that, compared to the susceptible colony Rockefeller, RecR present higher activity of glutathione S-transferases (GSTs), α- and β-esterases, and, to a lesser degree, mixed function oxidases (MFO). At the 14th or 17th generations, there was no cross resistance of these insects to deltamethrin, cypermethrin and malathion, while a low resistance level (RR = 3) was observed for pyriproxyfen, a juvenile hormone analogue. Experiments on resistance reversal, performed through three different field simulated schemes using the resistant strain, showed that temephos susceptibility can be recovered. The establishment of an A. aegypti colony resistant to temephos is extremely valuable for a deeper understanding of resistance mechanisms and thus for further improvements in control strategies against this vector. With the urgent need on improving methodologies to monitor resistance, molecular studies such as microarrays, and resistant colonies such as RecR will certainly hasten such studies.     

Effects of a one-week treatment with acid gastric inhibitors on Helicobacter pylori-infected mice

OBJECTIVE: Antiacid drugs, including omeprazole and ranitidine, were prescribed to Helicobacter pylori-infected subjects in combination with antibiotics during eradication treatment. Several reports suggest that these drugs have additional pharmacological properties, such as antineutrophil, antiapoptotic and antioxidant characteristics. The aim of this work was to study the effects of acid suppressive medication treatment in the H. pylori infection experimental model, focusing on possible additional pharmacological properties. MATERIAL AND METHODS: The ability of gastric acid suppression was assessed in pylorus-ligated animals. Gastric H. pylori colonization levels, myeloperoxidase (MPO) acitivity, macroscopic damage, Bax and Bcl-2 expression and DNA damage levels were assessed in C57BL/6-infected mice after treatment for one week with omeprazole (100 mg kg(-1)) or ranitidine (100 mg kg(-1)). RESULTS: Omeprazole treatment increased bacteria colonization and MPO activity in mice stomachs. Both antiacid drugs efficiently improved macroscopic damage, although only omeprazole restored the expression of the antiapoptotic Bcl-2 protein in gastric mucosa of infected animals. CONCLUSIONS: Some additional omeprazole-related properties, such as antineutrophil properties, were not observed in H. pylori-infected mice after one week of treatment, suggesting that this property is restricted to in vitro approaches. However, the antiapoptotic activity of omeprazole could be attributed to an ability to modify the protein expression of Bcl-2, decreased by H. pylori infection.     

Comparison Between Diltiazem and Cedilanid-D on Ventricular Rate Control of Atrial Fibrillation and Their Effect on Atrioventricular Conduction System.

Atrial fibrillation (AF) is the most commonsustained cardiac arrhythmia. Etiologies include coronary artery disease, hypertension, valvular heardisease, thyrotoxicosis and other cardiac and noncardiac conditions. Rapid ventricular rate during AFcan result in severe symptoms such as palpitation,dyspnea, and may precipitate heart failure, ischaemiaand syncope. The main therapeutic objective is rapid,efficient control of AF, thereby remit symptoms,prevent deterioration of heart functions and am…     

Occurrence of influenza B/Hong Kong-like strains in Brazil,during 2002

Through the influenza virus surveillance from January to October 2002, influenza B/Hong Kong-like strains circulating in the Southeast and Centre East regions of Brazil have been demonstrated. This strain is a variant from B/Victoria/02/88 whose since 1991 and until recently have been isolated relatively infrequently and have been limited to South-Eastern Asia. A total of 510 respiratory secretions were collected from patients 0 to 60 years of age, with acute respiratory illness, living in the Southeast and Centre East regions of Brazil, of which 86 (17.13%) were positive for influenza virus. Among them 12 (13.95%) were characterized as B/Hong Kong/330/2001; 3 (3.49%) as B/Hong Kong/1351/2002 a variant from B/Hong Kong/330/2001; 1 (1.16%) as B/Sichuan/379/99; 1 (1.16%) as B/Shizuoka/5/2001, until now. The percentages of cases notified during the surveillance period were 34.88%, 15.12%, 15.12%, 4.65%, 15.12%, 13.95%, in the age groups of 0-4, 5-10, 11-15, 16-20, 21-30, 31-50, respectively. The highest proportion of isolates was observed among children younger than 4 years but serious morbidity and mortality has not been observed among people older than 65 years, although B influenza virus component for vaccination campaign 2002 was B/Sichuan/379/99 strain. This was probably due to the elderly protection acquired against B/Victoria/02/88. In addition, in influenza A/Panama/2007/99-like (H3N2) strains 22 (25.58%) were also detected, but influenza A(H1N1) has not been detected yet.     

Cytokines and dietary energy restriction in stable chronic obstructive pulmonary disease patients.

Tumour necrosis factor (TNF)-alpha has been found to be increased in malnourished chronic obstructive pulmonary disease (COPD) patients; however, the main cause of this phenomenon remains undetermined. In normal subjects, TNF-alpha production may be induced by dietary energy deprivation. The aim of this study was to investigate if stable COPD patients present alterations of inflammatory mediators after 48 h of dietary energy restriction. Fourteen COPD patients were admitted to the hospital while receiving an experimental diet with an energy content of approximately one-third of their energy needs. Clinical evaluation, nutritional assessment and serum levels of interleukin (IL)-6, TNF-alpha and C-reactive protein, and secretion of TNF-alpha by peripheral blood monocytes were assessed on admission and after the experimental diet. For reference values of the laboratory parameters, blood was collected from 10 healthy, elderly subjects. COPD patients showed significantly higher serum concentrations of IL-6 than control subjects, however, the experimental diet was not associated with statistically significant changes in the inflammatory mediators. The findings of this study, although preliminary because of the limited degree and duration of the energy restriction, suggest that the elevated levels of tumour necrosis factor-alpha, previously described in undernourished or weight-losing chronic obstructive pulmonary disease patients, may not be linked to a decrease of dietary energy intake.