Reciprocal axo-axonal synapses between the common inhibitor and excitor motoneurons in crustacean limb muscles

Summary Nerve terminals of the common inhibitor motoneuron in a crab (Eriphia spinifrons) limb closer muscle and in a crayfish (Procambarus clarkii) limb accessory flexor muscle make neuromuscular synapses with the muscle membrane (postsynaptic inhibition) as well as axo-axonal synapses with the terminals of the excitatory axon (presynaptic inhibition). That transmission is from the inhibitor to the excitor terminals at these axo-axonal synapses is indicated by the occurrence on the inhibitor membrane of presynaptic dense bars denoting sites of transmitter release. Axo-axonal synapses with the opposite polarity, in which transmission is from an excitatory onto an inhibitory terminal, were occasionally seen either adjacent to or separate from the inhibitory axo-axonal synapse. Nerve terminals of the specific inhibitor in the crayfish opener muscle were seen to make numerous axo-axonal output synapses upon excitatory nerve terminals but excitor nerve terminals were not seen to make output synapses onto inhibitor terminals. Thus reciprocal axo-axonal synapses appear to be a feature of the common inhibitor but not of the specific inhibitor. The excitor-to-inhibitor component of these reciprocal synapses may serve to limit transmitter output in the common inhibitor axon by activating glutamate_B receptors which facilitate efflux of K⁺ and hyperpolarization of the membrane.     

Inherited prothrombotic defects in Budd-Chiari syndrome and portal vein thrombosis: a study from North India

We studied 57 patients with Budd-Chiari syndrome (BCS) and 48 with portal vein thrombosis (PVT) for underlying inherited prothrombotic defects such as protein C, protein S, and antithrombin III deficiencies. Genetic mutations for factor V Leiden, prothrombin gene 20210A, and methyltetrahydrofolate reductase (MTHFR) C677T were studied in 29 patients in each group. Inherited prothrombotic defects were detected in 16 (28%) of 57 patients with BCS and 7 (15%) of 48 patients with PVT. Factor V Leiden mutation was the most common prothrombotic defect in BCS (5/29 [17%]) followed by protein C deficiency (7/57 [12%]) and protein S deficiency (4/57 [7%]), whereas in PVT, protein C deficiency was the most common inherited prothrombotic defect (4/48 [8%]) followed by protein S deficiency (2/48 [4%]). The factor V Leiden mutation was detected in only 1 (3%) of 29 cases of PVT. The heterozygous MTHFR C677T mutation was detected in 7 (24%) of 29 patients with BCS and 6 (21%) of 29 patients with PVT. Antithrombin III deficiency, homozygous MTHFR C677T mutation, and prothrombin G20210A mutation were not detected in any patients.     

Emergence of a nephropathogenic avian infectious bronchitis virus with a novel genotype in India

We describe the emergence of a nephropathogenic avian infectious bronchitis virus (IBV) with a novel genotype in India. The Indian IBV isolate exhibited a relatively high degree of sequence divergence with reference strains. The highest homology was observed with strain 6/82 (68%) and the least homology with strain Mex/1765/99 (34.3%).     

Novel predictive risk factor for Erectile Dysfunction: Serum folic acid

The purpose of this study was to compare the serum Folic Acid (FA) levels in patients with Erectile Dysfunction (ED) and healthy controls and whether levels vary with its severity. The study was carried out on 77 sexually active individuals, out of which 41 complained of ED and 36 were apparently normal. Patients were excluded if they had any diseases known to cause ED. The severity was further categorised based on IIEF-5 scores. Blood serum levels of testosterone, lipid profile, random blood sugar, liver function test, renal function test and FA levels were obtained in each patient. Independent-samples t test of significance was used when comparing between two means. Pearson's correlation coefficient (r) test was used for correlating data. All clinical and biochemical parameters except FA were comparable in both the groups. FA levels were significantly decreased in ED group (5.29 vs. 10.8; p value = .004). Smoking habits were comparable between the groups, and FA levels did not vary among smokers and nonsmokers (p value = .46). Serum FA levels significantly declined with increasing severity of ED (8.28 vs. 5.56 vs. 4.37 vs. 3.5; p value < .001). Thus, decreased FA might possibly be one of the novel risk factors for ED.     

Bioavailability of curcumin: problems and promises

Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.     

The Case for Resource Sensitivity: Why It Is Ethical to Provide Cheaper,Less Effective Treatments in Global Health

When Dr. Hortense screens her patients in Chicago for cervical dysplasia and cancer, she conducts a pelvic exam, takes a sample of cervical cells, and sends them for Pap cytology and human papilloma virus DNA co‐testing. But when she conducts cervical cancer screening in Botswana, she employs a much simpler diagnostic strategy. She applies acetic acid to highlight precancerous lesions and visually inspects the cervix—a technique known as the VIA (visual inspection with acetic acid) method. She treats suspicious lesions with cryotherapy. There are multiple reasons that Dr. Hortense uses VIA in developing countries. It requires no specialized laboratory facilities or highly trained personnel. With immediate results, there is no delay in diagnosis and treatment, ensuring that patients are not lost to follow‐up. Most importantly, VIA is considerably cheaper than Pap and HPV co‐testing. This difference in care between Chicago and Botswana presents an ethical dilemma in global health: is it ethically acceptable to provide some patients cheaper treatments that are less effective or more toxic than the treatments other patients receive? We argue that it is ethical to consider local resource constraints when deciding what interventions to provide. The provision of cheaper, less effective health care is frequently the most effective way of promoting health and realizing the ethical values of utility, equality, and priority to the worst off.