Recurrent laryngeal nerve and the posterior fascial attachment of the thyroid gland.

An investigation based on dissection of cadaveric specimens was undertaken to obtain additional data on the relationships between the recurrent laryngeal nerve and the posterior fascial attachment of the thyroid gland. Ninety-four dissections were selected for detailed study. The posterior fascial attachment on each side was found to form two bands--a vertical band described previously and a horizontal band. The horizontal band was found to be present in all cases and to be constant in position. The posterior edge of the horizontal band followed posteriorly leads to the recurrent laryngeal nerve. The nerve always had a close relationship to the horizontal band and was often adherent to it. It is suggested that the use of the horizontal band to locate the recurrent laryngeal nerve would be of particular value when the inferior thyroid artery is absent, when the nerve is non-recurrent on the right side, or when there is distortion of the normal anatomy.     

Assessment of calcium dobesilate in diabetic retinopathy. A double-blind clinical investigation.

In this double-blind, randomized trial, which lasted for 2 years, the authors investigated the efficacy of calcium dobesilate on diabetic retinopathy. 68 patients (51 on the active substance, 17 on placebo) participated in the study. The statistical analysis of the results indicate that calcium dobesilate acts as a potent angioprotector, capable of preventing both intra and extraretinal hemorrhages. The drug also lowers the incidence of exudate formation and improves visual acuity.     

Temporary increase in forebrain norepinephrine turnover in mouse-killing rats

Increased forebrain norepinephrine levels and turnover occur in the aggressive mouse-killing rat 2 hr after a killing episode. These neurochemical effects persist for 24 hr and return to normal by 48 hr. Such changes appear to be related to the killing episode (i.e. stress) and unrelated to aggressiveness. Conceivably, activation or induction of tyrosine hydroxylase might be responsible for these effects.     

The impact of pharmacologic and genetic knockout of P-glycoprotein on nelfinavir levels in the brain and other tissues in mice

Insufficient concentrations of protease inhibitors such as nelfinavir may reduce the effectiveness of HIV dementia treatment. The efflux transporter mdr1 product P-glycoprotein (P-gp) has been demonstrated to play a role in limiting nelfinavir brain levels. The goal of this study was to compare the effect of GF120918 (10 mg/kg, IV), a P-gp inhibitor, on intravenous nelfinavir (10 mg/kg) in vivo disposition and tissue penetration in P-gp-competent mdr1a/1b (+/+) mice versus P-gp double knockout mdr1a/1b (-/-) mice. Intravenous administration with the P-gp inhibitor GF120918 to mdr1a/1b (+/+) mice increased nelfinavir concentrations over a range of 2.3- to 27-fold, whereas nelfinavir distribution in mdr1a/1b (-/-) mice was 2- to 16-fold higher than that in their wild counterparts. Nelfinavir levels after GF120918 coadministration were higher in the heart, liver, and kidneys than those detected with mdr1a/1b knockout mice. In contrast, mdr1a/1b knockout mice exhibited higher nelfinavir levels in the brain (16.1-fold vs. 8.9-fold increase) and spleen (4.1-fold vs. 2.3-fold increase) compared to pharmacological inhibition with GF120918 in wild mice. Most notably, GF120918 provided tissue-specific effects in mdr1a/1b knockout mice with enhanced (p < 0.05) drug accumulation in the brain ( approximately 21-fold) and heart (3.3-fold). Our results suggest mdr1a/1b-independant mechanisms may also contribute to nelfinavir tissue distribution in mice.     

NAT2*5/*5 genotype (341T>C) is a potential risk factor for schistosomiasis-associated bladder cancer in Egyptians

Arylamine N-acetyl transferase (NAT2) displays extensive genetic polymorphisms that affect the rates of acetylation of drugs and genotoxic compounds such as amine carcinogens. To investigate whether the slow acetylator genotype is a risk factor for development of bladder cancer following schistosomal infection of the urinary tract, the authors determined the frequencies of 3 common polymorphisms in the NAT2 gene (341T>C, 590G>A, and 282C>T), which are associated with impaired acetylation activity, in control subjects (n=61; mean age 34.3+/-9.2 years) and in schistosomiasis-associated bladder cancer patients (n=55; 52+/-10.9 years) from the Egyptian population. Genotyping was carried out using rapid cycle PCR on the LightCycler, and subjects were assigned to a slow, intermediate, or rapid acetylator phenotype on the basis of the genotypes. The frequencies of the mutant alleles observed in the controls from the present study were similar to those reported previously for both the Egyptian population and other Arab populations. Patients showed a higher prevalence (78.2%) of slow acetylator phenotype than controls (67.2%), but this did not reach statistical significance (P=0.19). However, there were significantly more individuals who were carriers of 2 mutant 341T>C alleles (NAT2*5/*5 genotype) in the patient group compared with controls (odds ratio 2.6, CI 1.02-6.67, P=0.026). The alloenzyme encoded by this allele has been shown to display a large reduction in its catalytic activity. In conclusion, these data suggest that the NAT2*5/*5 genotype is a potential risk factor for development of urinary bladder cancer in patients with prior schistosomiasis infection.