Cannabinoids and morphine differentially affect HIV-1 expression in CD4(+) lymphocyte and microglial cell cultures

The influence of substances of abuse on the progression of HIV-1 infection is controversial, and pharmacologic factors have been postulated as a potential explanation for conflicting data arising from epidemiological studies and animal models. In the present study, cell culture models of HIV-1 infection were used to test this hypothesis. The synthetic cannabinoid WIN 55,212-2 was found to potently inhibit HIV-1 expression in a concentration- and time-dependent manner in CD4(+) lymphocyte and microglial cell cultures. In sharp contrast, morphine either inhibited or stimulated viral expression, depending upon the time of drug exposure, and marked differences were observed between CD4(+) and microglial cells. Also, WIN 55,212-2 inhibited the stimulatory effect of morphine in HIV-1 infected CD4(+) cells. These in vitro findings support the notion that pharmacologic factors need to be considered in epidemiological studies and animal models that pertain to HIV-1 infection.     

Kappa-opioid receptor agonist suppression of HIV-1 expression in CD4+ lymphocytes

Synthetic kappa-opioid receptor (KOR) agonists have been shown to suppress HIV-1 expression in acutely infected macrophages. In the present study, we examined the effects of the KOR ligand trans-3,4-dichloro-N-methyl-N[2-(1-pyrolidinyl)cyclohexyl]benzeneaceamide methanesulfonate (U50,488) on HIV-1 expression in CD4+ lymphocytes, the main target cell of this virus. When U50,488 was added to activated CD4+ lymphocytes, HIV-1 expression was inhibited in a concentration- and time-dependent manner with maximal suppression (approximately 60%) at 10(-7) M U50,488. The KOR selective antagonist nor-binaltorphimine (nor-BNI) had no effect by itself on viral expression but blocked the antiviral property of U50,488, suggesting that U50,488 was acting via a KOR-related mechanism. Support for the involvement of KOR was provided by the findings that 34% of activated CD4+ lymphocytes were positive for KOR, using an immunofluorescence technique, and that seven additional synthetic KOR ligands also inhibited HIV-1 expression. The results of this study broaden understanding of the antiviral properties of KOR ligands to include cells outside of the nervous system and suggest a potential role for these agents in the treatment of HIV-1 infection.     

Spinal intramedullary tuberculoma requiring surgical treatment--case report

A 71-year-old male presented with multiple central nervous system tuberculomas including spinal intramedullary tuberculoma manifesting as occipitalgia and left hemiparesis. He had received medical treatment for lung and testis tuberculosis. Magnetic resonance imaging revealed an intramedullary lesion at the C-2 level as well as multiple small extramedullary and intracranial lesions. His neurological symptoms gradually worsened despite intensive antituberculous therapy. The C-2 intramedullary lesion responsible for left hemiparesis was surgically extirpated. Postoperatively, his neurological symptoms improved gradually, and no recurrence was evident at the resected site. Surgical intervention is mandatory in patients with intramedullary tuberculoma if neurological symptoms deteriorate or lesions enlarge despite continuous antituberculous therapy.     

Pharmacokinetics and influence of arbekacin on renal function in low-birth-weight infants

Arbekacin (ABK) is an aminoglycoside with excellent antibacterial activity against methicillin-resistantStaphylococcus aureus (MRSA). Although ABK is expected to be a useful drug for MRSA infection in newborns, there have been few reports concerning its pharmacokinetics, efficacy, and safety. Ten low-birth-weight infants were treated with ABK. Their mean gestational age was 29.4±5.3 weeks and their mean birth weight was 1204±532 grams. At the time of initial ABK administration, the mean postconceptional age was 33.9±4.2 weeks. ABK was infused over a period of 30 minutes every 12 hours at doses ranging between 2.2 and 3.1 mg/kg. Trough (predose) and peak (30 minute postdose) serum ABK concentrations were determined. TheN-acetyl-β-d-glucosaminidase (NAG) index (NAG:creatinine ratio) was measured before and after ABK therapy. The mean peak serum ABK concentration was 8.49±2.06 μg/mL and the mean trough concentration was 3.93±2.14 μg/mL, with a mean half-life of 11.4±6.1 hours. A significant negative correlation existed between postconceptional age and ABK half-life (r=0.64;P<0.05), and there was a positive correlation between postconceptional age and ABK clearance (r=0.83;P<0.05). The NAC index significantly increased after ABK therapy (P<0.05), and a significant positive correlation was found between the though level of ABK and the NAG index after ABK therapy (r=0.84;P<0.05). ABK, similar to other aminoglyoosides, should be used with caution in low-birth-weight infants with careful attention given to their renal function.