Infection by Mycobacterium tuberculosis promotes human alveolar macrophage apoptosis

The effect of Mycobacterium tuberculosis infection on the viability of healthy (control) human alveolar macrophages was evaluated by staining with ethidium homodimer and calcein to discriminate live from dead cells. Infection with M. tuberculosis H37Ra or H37Rv increased macrophage mortality at 6 days from the control level of 3.8% +/- 0.7% to 28.7% +/- 6.9% or 12.6% +/- 3.1%, respectively (P < 0.001 for comparisons of all conditions). A role for tumor necrosis factor alpha (TNF-alpha) in the M. tuberculosis-induced cytolysis of alveolar macrophages was demonstrated by increased cytotoxicity following the addition of exogenous TNF-alpha to the cultures and by enhancement of macrophage survival when M. tuberculosis-infected alveolar macrophages were treated with pentoxifylline or anti-TNF-alpha antibody. The cytolytic mechanism was determined to be apoptosis by the demonstration of a characteristic internucleosomal ladder of genomic DNA by agarose gel electrophoresis, by finding nuclear fragmentation and condensation by electron microscopy, and by in situ terminal transferase-mediated nick end labeling of fragmented DNA in alveolar macrophages infected with M. tuberculosis in vitro. The latter technique was employed to reveal extensive apoptosis within caseating granulomas from lung tissue samples from clinical tuberculosis cases. The induction of apoptosis in alveolar macrophages by M. tuberculosis may play a role in the macrophage-pathogen interaction of tuberculosis in vivo.     

Oxytocin blocks the development of heroin-enkephalin cross-tolerance in mice

The development of cross-tolerance to an analgesic effect has been observed between a mu-receptor agonist, heroin, and a delta-receptor agonist, Met2-Pro5-enkephalinamide. Repeated treatments with heroin twice a day for 4 days resulted in a decreased nociceptive effect to enkephalin on day 5. The enkephalin dose-response line was shifted to the right, considered a sign of the development of cross-tolerance. Peripheral treatment with oxytocin blocked the development of heroin-enkephalin cross-tolerance. A similar effect was observed after intracerebroventricular administration of oxytocin, supporting our assumption that oxytocin blocks the development of heroin-enkephalin cross-tolerance via CNS mechanisms.     

Biology of membrane transport proteins

Membrane transporter proteins are encoded by numerous genes that can be classified into several superfamilies, on the basis of sequence identity and biological function. Prominent examples include facilitative transporters, the secondary active symporters and antiporters driven by ion gradients, and active ABC (ATP binding cassette) transporters involved in multiple-drug resistance and targeting of antigenic peptides to MHC Class I molecules. Transported substrates range from nutrients and ions to a broad variety of drugs, peptides and proteins. Deleterious mutations of transporter genes may lead to genetic diseases or loss of cell viability. Transporter structure, function and regulation, genetic factors, and pharmaceutical implications are summarized in this review.     

Doppler ultrasonographic evaluation of blood flow in the superior mesenteric artery in celiac patients and in healthy controls in fasting conditions and after saccharose ingestion

We studied, by means of Doppler ultrasonography, the blood flow in the superior mesenteric artery in 12 untreated patients with celiac disease (nontropical sprue) and in 15 healthy controls; peak systolic velocity, end diastolic velocity, mean velocity, flow volume, and resistive index were measured in the fasting state and at regular intervals after ingestion of 0.5 liter of water containing 50 g of saccharose. Under fasting conditions, celiac patients showed peak systolic velocity, end diastolic velocity, mean velocity, and flow volume values significantly higher than those of normal subjects, whereas resistive index was significantly lower. After saccharose ingestion these parameters showed greater variations in normal subjects than in celiac patients. Fasting end diastolic velocity turned out to be the best parameter to distinguish celiac patients from healthy subjects. Doppler ultrasonography of the superior mesenteric artery could discriminate between normal subjects and celiac patients with overt disease. However, these data need further confirmation given the limited sample that we studied; moreover, the capability of this technique in distinguishing nontropical sprue from other gastrointestinal diseases that cause increasing splanchnic flow remains to be ascertained.     

Medicare spending for elderly beneficiaries who need long-term care

To better understand how elderly people with long-term care needs might be affected by Medicare's greater reliance on risk plans, we examine Medicare spending for this population using data from the Medicare Current Beneficiary Survey. Medicare spending for elderly people with functional limitations is substantially greater than for other beneficiaries, but highly variable. Medicare spends more, however, for community residents with moderate to severe functional limitations than for nursing home residents with similar degrees of limitation. These results raise concerns about the incentives of Medicare risk plans in caring for enrollees with long-term care needs.     

The routine sampling procedure for PKU should be changed. Venous puncture is less painful than heel lancing

All newborns in Sweden are screened for phenylketonuria (PKU), among other things, blood usually being sampled by heel lancing. Because it is unnecessarily painful, however, this form of sampling in newborns has recently been questioned. There is reason to recommend sampling from a dorsal hand vein as the method of choice for PKU screening purposes.     

Breast cancer among women exposed to polybrominated biphenyls

We conducted a nested case-control study with 1,925 women enrolled in a polybrominated biphenyl (PBB) registry to examine the association between breast cancer and serum PBBs. Twenty women who developed breast cancer were matched to 290 control subjects on sex, race, and age. Women with serum PBB levels of 2.0-3.0 parts per billion (ppb) [odds ratio (OR) = 3.5; 95% confidence interval (CI) = 0.9-13] or 4.0 ppb or greater (OR = 3.1; 95% CI = 0.8-12) had a higher estimated risk for breast cancer than women with less than 2.0 ppb. The odds ratios were unchanged when available breast cancer risk factors were included in the analysis.