Destabilization of tRNA3(Lys) from the primer-binding site of HIV-1 genome by anti-A loop polyamide nucleotide analog.

Initiation of human immunodeficiency virus type 1 (HIV-1) reverse transcription occurs by extension of the cellular tRNA3(Lys) which anneals to the primer-binding site (PBS) on the 5' non-translated region of the viral RNA genome. The A-rich sequence (A-loop) upstream of the PBS interacts with the anticodon loop of tRNA3(Lys) and has been proposed to be essential for conferring specificity to tRNA3(Lys) for priming the initiation of HIV-1 reverse transcription. We observed that polyamide nucleic acid targeted to the A-loop sequence (PNAAL) exhibits high binding specificity for its target sequence. The PNAAL pre-bound to the A-loop sequence prevents tRNA3(Lys) priming on the viral RNA consequently blocking in vitro initiation of reverse transcription. Further, PNAAL can efficiently disrupt the preformed [tRNA3(Lys)--viral RNA] complex thereby rendering it non-functional for reverse transcription. The endogenous reverse transcription in disrupted HIV-1 virions containing packaged tRNA3(Lys) and its replicating enzyme RT was significantly inhibited by PNAAL, thus providing direct evidence of the involvement of the A-loop region of viral RNA genome in tRNA3(Lys) priming process. These findings suggest the potential of the A-loop region as a critical target for blocking HIV-1 replication.

Primary hypercholesterolemia: effect of treatment on serum lipids, lipoprotein fractions, cholesterol absorption, sterol balance, and platelet aggregation.

The nonabsorbable bile acid sequestrant resin, colestipol, was administered to 16 patients with primary hypercholesterolemia, and its effect on serum lipids, lipoprotein fractions, and circulating platelet aggregate ratio and platelet aggregation in response to adenosine diphosphate (ADP) was compared with that of sitosterol. Cholesterol absorption and sterol balance studies were done in four of the subjects during the following treatment periods: diet alone, colestipol, and sitosterol. Total serum cholesterol was significantly reduced by colestipol but only slightly decreased by sitosterol. Combination treatment with colestipol and sitosterol was associated with a smaller decrease in serum cholesterol than was demonstrated with colestipol alone. Serum triglycerides tended to increase during colestipol therapy (this increase was not clinically significant) but showed a minimal nonsignificant decrease with sitosterol treatment. Colestipol decreased cholesterol absorption, whereas sitosterol slightly increased it. Fecal sterol excretion was increased with colestipol treatment but was minimally affected by administration of sitosterol. Low-density lipoprotein and high-density lipoprotein cholesterol significantly decreased with colestipol treatment. The circulating platelet aggregate ratio was significantly lower in the group of patients with hypercholesterolemia who received colestipol initially than in control subjects, but platelet aggregation in response to ADP was not significantly different between these two groups. No significant change in platelet aggregation was noted during colestipol or sitosterol treatment despite a significant decrease in total serum cholesterol with colestipol therapy, a suggestion that the platelet and lipid abnormalities are not interrelated.

Oral soft tissue manifestations and CD4 lymphocyte counts in HIV-infected children.

This study investigated the prevalence of oral soft tissue lesions in children infected with HIV and the relationship of CD4 lymphocyte levels with the prevalence of those lesions. Sixty HIV-positive children enrolled in the Children's Hospital AIDS Program (age 5.8 +/- 3 years) were selected for study. Only five subjects (8%) had healthy gingiva and a low mean plaque index (22%). The remainder had gingivitis or periodontitis with relatively high plaque indices (47, 55, and 94%, respectively). A declining CD4 lymphocyte count (1357 to 35) was associated with an increasing severity of gingival disease.

[Surgery of inguinal hernias in the geriatric patient]. / La chirurgia dell'ernia inguinale nel paziente geriatrico.

The Authors report a series of 73 elderly patients undergone to Lichtenstein hernioplasty with local anaesthesia. Treatment of inguinal hernia in emergency involves a high mortality; on the contrary, the lack of complications and a very good patient compliance shows that elective repair of inguinal hernia should be preferred and performed in the elderly.

High fiber diet in hyperlipemia. Comparison with cholestyramine treatment in type IIA hyperlipoproteinemia.

Fourteen patients with type IIa hyperlipoproteinemia were treated with a high fiber intake (powdered cellulose or soy hulls or both) for six months. Eight of the patients were treated with 16 g of cholestyramine resin daily without the high fiber intake for an additional six months. The cholesterol intake was comparable in both treatment programs. The mean serum cholesterol levels decreased during both, but the decrease occurred and was more pronounced in all patients treated with cholestyramine. Responsiveness to the high fiber diet was not related to an increased responsiveness to cholestyramine treatment. In most patients the serum triglyceride levels increased, and the fasting plasma glucose level did not change substantially during either treatment program. Both regimens were free of adverse side effects.