Acceleration of the Menstrual Cycle by Intercourse

Hazard statistics were applied to an extensive set of prospective data to test for an acceleration of the menstrual cycle by intercourse. Intercourse appeared to accelerate both the basal body temperature (BBT) shift and the onset of menses. Menses was accelerated more by a combination of follicular and luteal intercourse than by luteal intercourse alone (using the BBT shift as an ovulation indicator). The accelerator effects of intercourse therefore appear to cumulate across the menstrual cycle.     

Differential Regulation of Bax, Bcl-2, and Bcl-X Proteins in Focal Cortical Ischemia in the Rat

Focal ischemia in the parietal cortex of the rat results in massive neuronal death in the infarct zone and penumbra between 12 hours and 6 days after photothrombosis. To examine a possible role of Bcl-2 family proteins in this process of cell death, we investigated their expression by immunoblot assays and immunocytochemistry, and correlated expression patterns with TUNEL as well as morphological signs indicative of apoptosis. In the center of the lesion Bax immunostaining was increased in many degenerating neurons between 4 hours and 3 days after the induction of photothrombosis. At all time points examined, Bcl-2 and Bcl-X protein levels were markedly reduced in injured neurons as compared to the unlesioned side. At the border of the ischemic lesion, two areas were distinguished: 1 – 2 days after induction of photothrombosis, pyknotic cells located immediately adjacent to the lesion core displayed nuclear Bcl-X and Bax immunoreactivity. In contrast, large, morphologically intact neurons located more towards the healthy brain parenchyma displayed an increase in cytoplasmic Bcl-2 and Bcl-X proteins. Double staining for each of the Bcl-2 family proteins and TUNEL revealed that DNA strand breaks and nuclear fragmentation seen in cells located in the lesion core were often associated with increased levels of Bax, but not with elevated Bcl-2 or Bcl-X protein levels, suggesting a role for Bax in the induction of apoptotic death in these cells. The upregulation of Bcl-2 and Bcl-X expression in surviving neurons close to the penumbra might reflect an active survival mechanism that protects these neurons from cell death following a sublethal insult.     

Double-stranded RNA and bacterial lipopolysaccharide enhance sensitivit to TNF-{alpha}-mediated cell death

The effect of double-stranded RNA (dsRNA) and bacterial lipopolysaccharideon the sensitivity to tumor necrosis factor (TNF)--medlatedcell death was studied In an In vitro system. Since secretionof TNF- Is a part of the early host response to viral and bacterialinfection, we examined whether mimicking the Infection withviral and bacterial products could affect the response of cellsto TNF-. Incubation of WEHI 164 fibrosarcoma cells with dsRNAor lipopolysaccharide (LPS) significantly increased their sensitivityto TNF--mediated lysis and to TNF-secreting inflammatory T cell-mediatedlysis. Thus, these products could induce Increased sensitivityto TNF- In cells In an inflammatory focus, possibly contributingto selective elimination of Infected but not healthy cells bythis non-specific cytokine. Additionally, our data show thatboth dsRNA and LPS, as well as TNF- Itself, rapidly Induce nuclearfactor-xB (NF-*B), a DNA-bindlng protein Implicated In regulationof gene expression. We suggest that NF-xB could regulate genescrucial for the induction of cell death by TNF-.     

L-701,324, a selective antagonist at the glycine site of the NMDA receptor, counteracts haloperidol-induced muscle rigidity in rats

  Rationale: It has recently been suggested that the overactivity of glutamatergic neurotransmission may contribute to the pathophysiology of Parkinson’s disease. Therefore, a search for new compounds which block glutamatergic receptors and show antiparkinsonian properties in animal models of this disease seems to be justified. Objective: The aim of this study was to determine whether L-701,324 [7-chloro-4-hydroxy-3(3-phenoxy) phenylquinoline-2-(H)-one], a selective and full antagonist at the glycine site of the NMDA receptor, counteracts parkinsonian-like muscle rigidity and catalepsy induced by haloperidol in rats. Methods: The muscle tone was measured as the resistance developed to passive flexion and extension of the hind limb. Electromyographic (EMG) activity was additionally recorded in the gastrocnemius and tibialis anterior muscles. Results: L-701,324 (2.5–40 mg/kg IP) dose-dependently decreased the muscle tone enhanced by haloperidol (1–5 mg/kg IP). Likewise, the haloperidol-enhanced resting EMG activity and the EMG reflex response to passive movements were diminished by lower and almost abolished by higher doses of L-701,324. However, up to a dose of 20 mg/kg IP, L-701,324 did not influence haloperidol (0.5 mg/kg IP)-induced catalepsy. Moreover, L-701,324 (1.25–5 mg/kg IP) given alone or together with haloperidol (0.5–1 mg/kg IP) disturbed rotarod performance. Gross observation of behaviour indicated that rats injected with L-701,324 in doses equal to or higher than 5 mg/kg, alone or in combination with haloperidol, were markedly ataxic, i.e. rats showed signs of disturbed balance and loss of control over their hind limbs. Conclusions: The present study suggests that L-701,324 exhibits a beneficial action in the animal model of parkinsonian rigidity, but not that of parkinsonian akinesia. Nonetheless, this compound is not devoid of motor side-effects. Received: 1 February 1998 / Final version: 20 October 1998     

Increased rates of chromosome breakage in BRCA1 carriers are normalized by oral selenium supplementation.

Women who are born with constitutional heterozygous mutations of the BRCA1 gene face greatly increased risks of breast and ovarian cancer. The product of the BRCA1 gene is involved in the repair of double-stranded DNA breaks and it is believed that increased susceptibility to DNA breakage contributes to the cancer phenotype. It is hoped therefore that preventive strategies designed to reduce chromosome damage will also reduce the rate of cancer in these women. To test for increased mutagenicity of cells from BRCA1 carriers, the frequency of chromosome breaks was measured in cultured blood lymphocytes following in vitro exposure to bleomycin in female BRCA1 carriers and was compared with noncarrier relatives. The frequency of chromosome breaks was also measured in BRCA1 carriers following oral selenium supplementation. Carriers of BRCA1 mutations showed significantly greater mean frequencies of induced chromosome breaks per cell than did healthy noncarrier relatives (0.58 versus 0.39; P < 10(-4)). The frequency of chromosome breaks was greatly reduced following 1 to 3 months of oral selenium supplementation (mean, 0.63 breaks per cell versus 0.40; P < 10(-10)). The mean level of chromosome breaks in carriers following supplementation was similar to that of the noncarrier controls (0.40 versus 0.39). Oral selenium is a good candidate for chemoprevention in women who carry a mutation in the BRCA1 gene.     

Expression of BAG-1 and BcL-2 Proteins Before and After Neoadjuvant Chemotherapy of Locally Advanced Breast Cancer

It has been suggested that expression of anti-apoptotic proteins such as Bcl-2 or BAG-1 may confer cellular resistance to chemotherapy. A corollary of this hypothesis is that expression of these proteins may predict clinical response to treatment and that Bcl-2- or BAG-1-positive cells may selectively be enriched in postchemotherapy tissue specimens. The goal of this exploratory pilot study was to assess these two predictions by using immunohistochemistry in 29 paired pre- and postchemotherapy breast tissue specimens obtained from patients who underwent preoperative doxorubicin-based chemotherapy. All breast cancers expressed BAG-1 protein, and, in individual tumors, 40-100% of neoplastic cells stained positive for this protein. Homogenous cytoplasmic staining was typically observed, though neoplastic cells also showed nuclear staining in many specimens. We found no correlation between prechemotherapy expression of BAG-1 and subsequent pathological response to cytotoxic therapy. Paired pre- and posttreatment specimens showed similar levels of BAG-1 expression when residual tumor could be assessed. Bcl-2 was expressed in 55% of cancers and was localized to the cytoplasm. Absence of Bcl-2 expression in prechemotherapy specimens was associated with more frequent complete pathological response (58% vs. 20%; p = 0.04). However, similar to BAG-1, no difference between pre- and posttherapy expression of Bcl-2 was observed in neoplastic cells in paired tissue specimens. These observations suggest that BAG-1 contributes an important cellular function to breast epithelial cells, which is reflected by its ubiquitous expression in these tissues. However, it does not appear to determine response to doxorubicin-based chemotherapy. In contrast, lack of Bcl-2 expression was associated with a higher probability of complete pathological response to doxorubicin-based chemotherapy.     

Immunosuppressive Compounds Exhibit Particular Effects on Functional Properties of Human Anti-Aspergillus TH1 Cells

Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at high risk for invasive aspergillosis. Whereas adoptive immunotherapy transferring donor-derived anti-Aspergillus T_H1 cells has been shown to be beneficial for HSCT recipients suffering from invasive aspergillosis, little is known about the impact of commonly used immunosuppressants on the functional properties of anti-Aspergillus T_H1 cells. Anti-Aspergillus T_H1 cells were coincubated with different concentrations of methylprednisolone, cyclosporine (CsA), mycophenolic acid (MPA), the active component of mycophenolate mofetil, and rapamycin. Immunosuppressants were tested in concentrations reflecting common target levels in serum and in significantly lower and higher concentrations. Apoptosis of anti-Aspergillus T_H1 cells, as well as proliferation and production of gamma interferon (IFN-γ) and CD154 upon restimulation, was evaluated in the presence and absence of immunosuppressive compounds. All dosages of CsA, MPA, and methylprednisolone significantly decreased the number of viable anti-Aspergillus T_H1 cells in the cell culture, which was due partly to an impaired proliferative capacity of the cells and partly to an increased rate of apoptosis. In addition, CsA significantly decreased the number of IFN-γ-producing cells and had the highest impact of all immunosuppressants on IFN-γ levels in the supernatant. CsA also significantly decreased the expression of CD154 by anti-Aspergillus T_H1 cells. Variant dosages of immunosuppressants exhibit particular effects on essential functional properties of anti-Aspergillus T_H1 cells. Our findings may have an important impact on the design of clinical trials evaluating the therapeutic benefit of anti-Aspergillus T_H1 cells in allogeneic HSCT recipients suffering from invasive aspergillosis.     

Enrichment of spreadable fats with polyunsaturated fatty acids omega-3 using fish oil

Polyunsaturated fatty acids of the omega-3 series, especially very long chain – eicosapenta- and docosahexaenoic acid (EPA, DHA) – exert a strongly desirable influence on health. However, their intake with the western-style diet is usually too low which favours development of many diseases (CVD, cancers, allergies, etc.). Nowadays elevation of EPA and DHA intake is commonly recommended, but almost the only dietary source of them is seafoods, especially fish. A new way to increase the intake of long-chain omega-3 without radical changes of eating patterns is enrichment of regularly consumed foods with unhydrogenated fish oil. The aim of this study was to establish sensory and nutritionally acceptable enrichment level of low-calorie spreadable fats (soft margarine and mix of butter and vegetable oil) with EPA and DHA by addition of fish oil preparations (ROPUFA – 30% EPA, DHA and MARITEX – 10%), and evaluation of the stability of enriched spreads during storage (sensory and chemical). It was shown that tested spreadable fats might be enriched up to 1% EPA, DHA (i.e. 3% ROPUFA, 8% MARITEX), and that this had no significant influence on sensory acceptability. Both used fish oils which exerted similar influence on the quality of fats. An enriched mix of butter and vegetable oil and margarine may be stored up to 3 and 6 weeks respectively without significant decrease of quality. Peroxide value and acid numbers were not much affected by enrichment and storage. Daily portion (25–30 g/day) of spreadable fats enriched on the level established in the study may provide 0.2–0.3 g EPA, DHA, significantly increasing the amount of long-chain omega-3 in the diet above those eaten normally.