Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrugs of 5-aminosalicylic acid for colon-specific drug delivery in inflammatory bowel disease

Colon-specific mutual azo prodrugs of 5-aminosalicylic acid with essential amino acids were synthesized for the management of inflammatory bowel disease. The structures were confirmed by elemental and spectral analyses. 85–88% release of 5-aminosalicylic acid was achieved in rat fecal matter with half-lives ranging from 140 to 160 min, following first order kinetics. The prodrugs exhibited comparable ameliorating effect as that of sulfasalazine on trinitrobenzenesulfonic acid-induced experimental colitis in rats with a better safety profile.     

Prodrug strategies for antihypertensives

There is a great emphasis on research to discover methods aimed at enhancing the efficacy of drugs and reducing their toxicity and unwanted side effects. Prodrugs are biologically inactive compounds that are converted to actual drug molecule, through biotransformation, that combine with the receptors to produce the biological action. Prodrugs can thus be considered as drugs containing specialized nontoxic protective groups utilized in a transient manner to alter or eliminate the undesirable properties of the parent drug molecule. Hypertension is one of the leading risk factors for cardiovascular disease and represents a major health and economic burden. Most of the drugs for cardiovascular diseases have low oral bioavailability, short duration of action, first pass metabolism and variable lipohilicities. Out of the need to overcome these limitations, various prodrugs have been designed for antihypertensive agents. This review extensively focuses on various strategies used for design and development of prodrugs for the various classes of antihypertensives, emphasizing on the details regarding the need for prodrug synthesis for each class, structure, type of modification and goal achieved. It also provides an insight into the major advances in the field of antihypertensive prodrug research.     

Noncompaction of Ventricular Myocardium Associated With Hypertrophic Cardiomyopathy and Polycystic Kidney Disease

Noncompaction of ventricular myocardium (NVM), a relatively new diagnostic entity, is described as an arrest in the process of compaction of myocardial fibers, which results in a prominent trabecular network and deep intertrabecular recesses. Its coexistence with other cardiac anomalies like hypertrophic obstructive cardiomyopathy (HOCM) or polycystic kidney disease (PKD) had been reported in the past. We report the first case with all 3 different inherent conditions (NVM, HOCM, and PKD) manifesting in 1 patient. A 37-year-old man was referred for evaluation of a heart murmur. His medical history was positive for paroxysmal atrial fibrillation. Physical examination revealed a grade 3/6 systolic murmur loudest along the left sternal border accentuating on Valsalva maneuver. Echocardiography revealed HOCM. Cardiac magnetic resonance confirmed the presence of HOCM with the incidental finding of NVM and PKD. This case raises the possibility of genetic mutation common to these 3 clinical entities or 2 different gene mutations existing in the same individual.     

A novel technique for peripheral nerve repair

OBJECTIVE: To evaluate a novel technique for the repair of neural deficits using a single fascicle to bridge an injury in the rat sciatic nerve. STUDY DESIGN: Twenty-four male Lewis rats were divided into four groups as follows: group 1 (control group), 1.5-cm deficit without repair; group 2, conventional epineural repair with autografts (100% diameter); group 3, nerve repair with large single autograft fascicle (50% diameter); and group 4, nerve repair with small single autograft fascicle (25% diameter). METHODS: Nerve regeneration was evaluated at 3, 6, and 12 weeks by somatosensory evoked potential (SSEP) evaluation and standardized pin-prick and toe-spread tests. Nerve samples were harvested at 12 weeks and stained with toluidine blue to assess the total number of myelinated axons, axon area, and myelin sheath thickness. RESULTS: In group I, the pin-prick and toe-spread tests showed no response at 3, 6, and 12 weeks. Rats in groups 3 and 4 demonstrated significantly better pin-prick test results and a trend toward better toe-spread test responses compared with conventional-repair animals. The SSEP evaluations displayed nondiagnostic waves in rats in group 1 rats. There was no evidence that the other surgery groups differed significantly in median SSEP latencies. Histological evaluation revealed fibrosis in rats in group 1 rats and a significantly higher median number of axons and myelin thickness in the small single fascicle (1296 axons and 4.22 microm, respectively) and large fascicle (2682 axons and 4.62 microm, respectively) groups compared with the conventional autograft group (630 axons and 2.93 microm, respectively). The small fascicle group had a significantly greater mean axon area (58.59 micro m2) than the large fascicle (29.66 micro m2) and conventional autograft (25.35 micro m2) groups. CONCLUSIONS: Peripheral nerve repair using a single fascicle graft resulted in better functional recovery and morphometric outcome without a significant difference in electrophysiological status compared with conventional nerve repair. This technique may provide expanded sources of nerve autografts and alleviate the morbidity of harvesting peripheral nerves from multiple sites for individuals with extensive peripheral nerve injuries.     

Reproductive Life Planning: A Cross-Sectional Study of What College Students Know and Believe

Objectives The Centers for Disease Control and Prevention recommends a reproductive life plan (RLP) to promote individual responsibility for preconception health. The objectives of this study were to determine existing awareness of RLPs in a cohort of reproductive-age adults and to evaluate their knowledge level and beliefs about reproductive life planning. Methods We performed a cross-sectional survey study of adults ages 18–40 years old seeking care at the student health center of a large public university. Participation was voluntary. Survey responses were analyzed by age and gender. Results A total of 559 surveys were collected and analyzed. Only 24 % of participants had heard of an RLP although a majority (62.9 %) agreed that it is important to develop an RLP. Most respondents (85.4 %) preferred to receive information about reproductive life planning from a primary care provider or obstetrician-gynecologist, while only 4.2 % of patients surveyed reported ever being actually asked about an RLP by their healthcare provider. Among those who agreed that an RLP was important, knowledge of specific aspects of an RLP was lacking. Conclusions In our cohort of reproductive-age adults, general health literacy regarding RLPs was poor. Most of the young adults who responded to our survey did not know what an RLP was and even fewer had ever discussed one with their health provider.     

Tender growth on toe

A 50-year-old Caucasian man came to the dermatology clinic with a tender growth on his great toe. He first noticed it a year earlier after sustaining trauma to the area. The growth had been getting bigger and had intermittently bled. It had also oozed, so his primary care physician treated it as an infection with topical antibiotics, followed by several courses of oral antibiotics. Despite therapy, the lesion continued to grow and the patient was referred to us. The patient had a 3.4-cm-by-1.8-cm exophytic erythematous nodule on the left lateral great toe. What is your diagnosis? How would you manage this condition?     

Vitamin D status,determinants and relationship with biochemical profile in women with Type 2 Diabetes Mellitus in Delhi,India

ObjectiveTo determine the burden of vitamin D deficiency and its determinants and to assess the relationship of 25 hydroxycholecalciferol (25-OHD) levels with biochemical parameters linked to health outcomes in women with Type 2 Diabetes Mellitus (T2DM).Material and methodsThis was a hospital based cross-sectional study in the diabetes out-patient department clinic of a major tertiary care hospital in Delhi, India. Adult women with T2DM on treatment for at least 6 months were included in this study. The women who have been given Vitamin D supplementation during the past 6 months were excluded. We assessed Serum 25-OHD, HbA1c, lipid profile and fasting plasma glucose in the patients through standardized laboratory methods.ResultsOne hundred women with T2DM were enrolled of which 22 (22%) had good glycemic control (HbA1c < 7%). Vitamin D deficiency was seen among 77 (77%) and insufficiency among 16 (16%) of the recruited subjects. Younger age group (31–45 years) and illiteracy was significantly associated with vitamin D deficiency (p < 0.05). No association was found between Vitamin D deficiency and HbA1c levels.ConclusionVitamin D deficiency is highly prevalent among women with T2DM. Illiteracy and young age were major determinants of vitamin D deficiency indicating they need special attention and Vitamin D supplementation.     

Anti-Pfs25 Human Plasma Reduces Transmission of Plasmodium falciparum Isolates That Have Diverse Genetic Backgrounds

Pfs25 is a leading candidate for a malaria transmission-blocking vaccine whose potential has been demonstrated in a phase 1 trial with recombinant Pfs25 formulated with Montanide ISA51. Because of limited sequence polymorphism, the anti-Pfs25 antibodies induced by this vaccine are likely to have transmission-blocking or -reducing activity against most, if not all, field isolates. To test this hypothesis, we evaluated transmission-blocking activities by membrane feeding assay of anti-Pfs25 plasma from the Pfs25/ISA51 phase 1 trial against Plasmodium falciparum parasites from patients in two different geographical regions of the world, Thailand and Burkina Faso. In parallel, parasite isolates from these patients were sequenced for the Pfs25 gene and genotyped for seven microsatellites. The results indicate that despite different genetic backgrounds among parasite isolates, the Pfs25 sequences are highly conserved, with a single nonsynonymous nucleotide polymorphism detected in 1 of 41 patients in Thailand and Burkina Faso. The anti-Pfs25 immune plasma had significantly higher transmission-reducing activity against parasite isolates from the two geographical regions than the nonimmune controls (P < 0.0001).