Properties of a new, long-lasting vaginal delivery system (LASRS) for contraceptive and antimicrobial agents

In view of the need for improved vaginal formulations that are contraceptive, that may prevent transmission of sexually transmitted infections, or both, a new delivery system (base formulation; called Long Acting, Sustained Release of Spermicide, or LASRS) was developed that contains bioadhesive and other ingredients with a long history of safety, and was designed to provide long-lasting vaginal retention of the formulation and to minimize possible vaginal irritation caused by incorporated active ingredients. Nonoxynol-9 (N-9) was added as an active ingredient to study the vaginal irritating properties of the formulation and to assess its long-term effectiveness by postcoital spermicidal tests. In the first series of experiments, in vitro studies showed that the formulation spreads rapidly over a cellulose membrane, forming a bioadhesive layer that remained for at least 12 hours. The second series of experiments addressed the safety of the LASRS suppository in rabbits and primates. Even with a very high concentration of N-9 (20.5%), LASRS caused only mild/moderate but acceptable irritation in the rabbit. No vaginal irritation occurred in the primate at an even higher concentration (22.5%). During the third series of experiments, the long-lasting vaginal retention properties were evaluated by postcoital spermicidal tests in the primate. LASRS with N-9 was highly spermicidal even when mating was delayed for 12 hours after placement of the formulation. Spermicidal activity was also observed when 1) mating was delayed for 24 hours after insertion of the formulation, and 2) if the females were mated 2 or even 3 times without reinsertion of the suppository before collection of the vaginal contents. In the final series of tests, the postcoital spermicidal properties of menfegol, another cytotoxic spermicide, were evaluated as were several modifications in the base formulation. Menfegol produced essentially the same results as N-9. Altering the base formulation proved to be nonbeneficial because a decrease in the long-term spermicidal effectiveness was obtained. These results suggest that the LASRS suppository has good vehicle properties for the delivery of active ingredients to the vagina.     

Changes in motion characteristics, plasma membrane integrity, and acrosome morphology during cryopreservation of buffalo spermatozoa

Motion characteristics, plasma membrane integrity, and acrosome morphology of buffalo spermatozoa after different stages of cryopreservation (ie, dilution, cooling to 4 degrees C, equilibration at 4 degrees C, and freezing and thawing) were examined. Semen ejaculates from 4 buffalo bulls were pooled (n = 5), diluted in tris-citric acid extender, cooled to 4 degrees C over 2 hours, equilibrated at 4 degrees C for 4 hours, dispensed into 0.5-mL straws, and frozen in a programmable cell freezer before plunging into liquid nitrogen. Frozen semen was thawed at 37 degrees C for 15 seconds. After completion of each stage, sperm motion characteristics, plasma membrane integrity, and acrosomal morphology were determined using computer-assisted semen analysis, hypo-osmotic swelling assay, and phase-contrast microscopy, respectively. Data were presented as mean +/- standard error of the mean. Visual and computerized motility did not differ due to dilution, cooling, or equilibration (77.3% +/- 2.3% and 90.5% +/- 1.2%, respectively), but was reduced (P < .05) after freezing and thawing (53.0% +/- 4.6% and 48.6% +/- 6.5%, respectively). Linear motility of spermatozoa was lower (P < .05) after dilution or equilibration (56.2% +/- 2.4%) than after cooling or freezing and thawing (79.6% +/- 1.4%). Sperm curvilinear velocity was reduced (P < .05) from 112.4 +/- 5.3 microm/sec after dilution to 96.0 +/- 5.8 microm/s after cooling, and from 87.6 +/- 4.1 microm/s after equilibration to 69.4 +/- 2.0 microm/s after freezing and thawing. Sperm lateral head displacement differed (P < .05) after each stage (ie, dilution, 3.9 +/- 0.2 microm; cooling, 2.3 +/- 0.2 microm; equilibration, 3.1 +/- 0.3 microm; and freezing and thawing, 1.7 +/- 0.2 microm). Spermatozoa with intact plasma membranes were 80.2% +/- 3.9% after dilution, reduced (P < .05) to 60.4% +/- 5.6% after equilibration, and then to 32.6% +/- 3.8% after freezing and thawing. The percentage of spermatozoa with normal acrosomes remained higher after dilution, cooling, or equilibration (73.2% +/- 2.4%) than after freezing and thawing (61.8% +/- 2.4%; P < .05). In conclusion, the maximal damage to the motility apparatus, plasma membrane, and acrosomal cap of buffalo spermatozoa occurs during freezing and thawing followed by equilibration.     

Living a 'normal' life: young people coping with thalassaemia major or sickle cell disorder

This qualitative paper explores the strategies and resources young people use to cope with sickle cell disorder or thalassaemia major, two haemoglobin disorders with serious implications for health and survival. By focusing on coping strategies, we explore how young people attempt to take control over their lives. The respondents, largely of South Asian and African Caribbean origin, aged between 10 and 19 years, valued maintaining a normal' life and struggled to achieve this normalcy. Strategies were employed to minimise difference from peers but these strategies remained vulnerable. Coping occurred in a dynamic space, involving negotiation and engagement with both personal and structural factors. Threats to normalcy did not always reside in the condition; life transitions, changes in social relationships and racist. disablist or sexist marginalisation also threatened coping strategies.     

Twin gestation in a woman with a uterus didelphys. A case report

BACKGROUND: Twin gestation in a uterus didelphys is a rare condition, and the preferred labor course for these patients is unclear. CASE: A woman with a uterus didelphys presented at 14 weeks' gestational age. Serial ultrasound examinations demonstrated normally growing, diamniotic, dichorionic twins situated one in each uterine horn. The prenatal course was marked by intrauterine growth retardation, elevated liver functions and significant proteinuria. At 31 weeks' gestation, labor was induced; however, due to chorioamnionitis and arrest of cervical dilatation, cesarean section was performed 23 hours after rupture of membranes, and two viable female infants (1,480 and 1,421 g) were delivered. CONCLUSION: Twin gestation in a uterus didelphys is a rare condition, in which a trial of labor may be offered, with careful monitoring of both fetuses.     

Localised Wegener's granulomatosis in otolaryngology: a review of six cases

Wegener's granulomatosis (WG) is a necrotising granulomatous disease affecting the upper and/or lower respiratory tracts and is associated with focal glomerulonephritis. Formerly believed to be a multisystem disease, a localised form (LWG) is now recognised as a distinct subtype. We describe 6 cases of LWG with no renal or pulmonary involvement detected at the presentation or during follow-up. The total follow-up period ranged from 3 to 7 years in 5 cases. The diagnosis was based on clinical features, antineutrophil cytoplasmic antibody test and histological findings (necrotising granulomatous vasculitis, epithelioid granulomas with varying degrees of chronic inflammatory cells). All patients responded to standard immunosuppressive treatment. Our cases highlight the predilection of LWG for the head and neck region and hence these patients frequently present in the ENT departments. LWG has been discussed as a subtype of WG with a better prognosis and the previous literature has been reviewed on this subject. A high index of suspicion helped by serology and histology enables an early diagnosis, and commencement of proper treatment can prevent the irreversible destructive lesions.     

Recombinant human tumor necrosis factor alpha does not potentiate cell killing after photodynamic therapy with a silicon phthalocyanine in A431 human epidermoid carcinoma cells

Photodynamic therapy (PDT) is a novel cancer treatment utilizing a photosensitizer, visible light and oxygen. PDT with the silicon phthalocyanine Pc 4, a new photosensitizer, is highly effective in cancer cell destruction and tumor ablation. The mechanisms underlying cancer cell killing by PDT are not fully understood. Tumor necrosis factor alpha (TNF) is a multifunctional cytokine that has been implicated in photocytotoxicity. We asked whether recombinant human TNF (rhTNF) affects Pc 4-PDT cytotoxicity in A431 human epidermoid carcinoma cells. Co-treatment of A431 cells with various doses of Pc 4-PDT and a sub-lethal rhTNF dose led to a sub-additive reduction in cell survival. In addition, in the presence of Pc 4-PDT or rhTNF, caspase-3 activity and apoptosis were induced. The combined treatment, however, did not potentiate either caspase-3 activity or apoptosis. Similar to previous findings we observed that Pc 4-PDT initiated a time-dependent extracellular TNF accumulation. The data suggest that: a) PDT and rhTNF induce cancer cell killing through different mechanisms; and b) Pc 4-PDT-induced TNF production is a stress response that may not directly affect photocytotoxicity.     

Inhibition of macrophages with gadolinium chloride alters intercellular adhesion molecule-1 expression in the liver during acute endotoxemia in rats

Cell adhesion molecules are important for localized accumulation of phagocytes at sites of tissue damage. In the present studies, we analyzed the effects of blocking hepatic macrophages on expression of beta2 integrins and intercellular adhesion molecule-1 (ICAM-1) adhesion molecules on liver cells during acute endotoxemia. Flow cytometric analysis revealed distinct subpopulations of macrophages from control animals that varied on the basis of their size and density. In contrast, hepatocytes and endothelial cells were relatively homogeneous. Treatment of rats with endotoxin (5 mg/kg, intravenously) resulted in a time-dependent increase in the percentage of small, dense macrophages and a progressive loss of larger, less-dense cells. In contrast, no major effects were observed on the physical properties of hepatocytes or endothelial cells. ICAM-1 was found to be constitutively expressed on endothelial cells and hepatocytes, as well as on macrophages. Induction of acute endotoxemia resulted in a time-dependent increase in ICAM-1 expression on hepatocytes, which was observed within 3 hours and reached a maximum after 24 hours. An increase in ICAM-1 expression was also observed on endothelial cells and on macrophages at 3 hours, followed by a decrease at 24 to 48 hours. Macrophages and endothelial cells also constitutively expressed beta2 integrins. Induction of acute endotoxemia had no effect on beta2 integrin expression by these cells. Pretreatment of rats with gadolinium chloride (GdCl3), a macrophage inhibitor known to block endotoxin-induced liver injury, abrogated the effects of endotoxin on ICAM-1 expression by hepatocytes and macrophages. In contrast, ICAM-1 expression on endothelial cells increased. Interestingly, treatment of rats with GdCl3 alone resulted in a marked increase in expression of ICAM-1 on endothelial cells and hepatocytes, and of beta2 integrins on macrophages and endothelial cells. Taken together, these data suggest that ICAM-1 is involved in mediating macrophage adherence and accumulation in the liver during endotoxemia. Furthermore, macrophages appear to regulate expression of this cell adhesion molecule on parenchymal cells.