Further observations on the immunological induction of DNA synthesis in mouse peritoneal macrophages. Role of products of activated lymphocytes.

Subcutaneous injection of ovalbumin (OA) into mice immunized with OA in Freund's complete adjuvant was followed by an increase in the numbers of peritoneal macrophages synthesizing DNA, determined by autoradiography. The effect was immunologically specific. The increase was followed by an increase in the numbers of peritoneal macrophages; the numbers of peritoneal lymphocytes also increased. Injection of OA into immunized or normal mice was followed by a blood monocytosis. Increased DNA synthesis, determined by liquid scintillation counting, occurred in spleen or lymph node cells from immunized mice, cultured with OA. Diluted supernatants from such cultures, injected intravenously into normal mice, caused increases in the numbers of DNA-synthesizing peritoneal macrophages. Similarly, supernatants from concanavalin A stimulated spleen cells, freed of Con A, also caused an increase in DNA-synthesizing macrophages.     

Tuft-to-capsule adhesions and their precursors: differences between the vascular and tubular poles of the human glomerulus

Human glomerular capillary tufts were removed by microdissection and scanning electron microscopy was used to examine the surface of the capillary tuft and the interior of its Bowman's capsule in order to identify connections between the tuft and capsule. Glomeruli were examined in histologically normal renal cortex from 12 kidneys removed for tumour and 12 renal allografts removed for end-stage rejection. In normal kidney, the glomerular tuft was connected to Bowman's capsule by single podocytes and their processes. At the vascular pole, these were predominantly associated with parietal podocytes which lined Bowman's capsule. At the tubular pole, occasional podocytic processes derived from the capillary tuft bridged Bowman's space and connected to Bowman's capsule where there were no parietal podocytes. These podocytic connections were also found in all rejected transplants, but in addition adhesions were identified which consisted of thicker connections between the tuft and capsule. At the vascular pole, tuft-to-capsule adhesions were found in all 12 kidneys; these were always associated with parietal podocytes. Tubular pole adhesions were identified in ten of the 12 transplants. They were associated with abnormal squamous cells, but not with parietal podocytes. When the capillary tuft herniated into the proximal tubule, the tuft sometimes formed an adhesion with the origin of the proximal tubule. These observations suggest that podocyte connections between the glomerular tuft and Bowman's capsule may be precursors of glomerular adhesions at the vascular pole. Since tuft-to-capsule adhesions at the vascular pole differ morphologically from those at the tubular pole, this may reflect different pathogenetic mechanisms at the opposite poles of the glomerulus. © 1998 John Wiley & Sons, Ltd.     

Neuroprotective Efficacy of Mitochondrial Antioxidant MitoQ in Suppressing Peroxynitrite-Mediated Mitochondrial Dysfunction Inflicted by Lead Toxicity in the Rat Brain

Lead (Pb) is one of the most pollutant metals that accumulate in the brain mitochondria disrupting mitochondrial structure and function. Though oxidative stress mediated by reactive oxygen species remains the most accepted mechanism of Pb neurotoxicity, some reports suggest the involvement of nitric oxide (^?NO) and reactive nitrogen species in Pb-induced neurotoxicity. But the impact of Pb neurotoxicity on mitochondrial respiratory enzyme complexes remains unknown with no relevant report highlighting the involvement of peroxynitrite (ONOO^?) in it. Herein, we investigated these effects in in vivo rat model by oral application of MitoQ, a known mitochondria-specific antioxidant with ONOO^? scavenging activity. Interestingly, MitoQ efficiently alleviated ONOO^?-mediated mitochondrial complexes II, III and IV inhibition, increased mitochondrial ATP production and restored mitochondrial membrane potential. MitoQ lowered enhanced caspases 3 and 9 activities upon Pb exposure and also suppressed synaptosomal lipid peroxidation and protein oxidation accompanied by diminution of nitrite production and protein-bound 3-nitrotyrosine. To ascertain our in vivo findings on mitochondrial dysfunction, we carried out similar experiments in the presence of different antioxidants and free radical scavengers in the in vitro SHSY5Y cell line model. MitoQ provided better protection compared to mercaptoethylguanidine, N-nitro-L-arginine methyl ester and superoxide dismutase suggesting the predominant involvement of ONOO^? compared to ^?NO and O₂ ^??. However, dimethylsulphoxide and catalase failed to provide protection signifying the noninvolvement of ^?OH and H₂O₂ in the process. The better protection provided by MitoQ in SHSY5Y cells can be attributed to the fact that MitoQ targets mitochondria whereas mercaptoethylguanidine, N-nitro-L-arginine methyl ester and superoxide dismutase are known to target mainly cytoplasm and not mitochondria. Taken together the results from the present study clearly brings out the potential of MitoQ against ONOO^?-induced toxicity upon Pb exposure indicating its therapeutic potential in metal toxicity.     

Synthesis and evaluation of the cytotoxicities of tetraindoles: observation that the 5-hydroxy tetraindole (SK228) induces G₂ arrest and apoptosis in human breast cancer cells

Current chemical and biological interest in indole-3-carbinol (I3C) and its metabolites has resulted in the discovery of new biologically active indoles. As part of a program aimed at the development of indole analogues, tetraindoles 1-15 were prepared and their antiproliferative effects on human breast cancer cells were evaluated. The results show that the 5-hydroxy-tetraindole 8 (SK228) has optimum antiproliferative activity against breast adenocarcinoma (MCF 7 and MDA-MB-231) cells and that this activity involves G(2)-phase arrest of the cell cycle with a distinctive increase in the expression of cyclin B1 and phospho-cdc2. Further observations suggest that 5-hydroxy-tetraindole 8 induces apoptosis through externalization of membrane phosphatidylserine, DNA fragmentation, and activation of caspase-3. Given the fact that I3C and its metabolites have been shown to improve therapeutic efficacy and to have a broad range of antitumor activities in human cancer cells, the current findings have important pharmacological relevance as they open a promising route to the development of a potential chemotherapeutic application of tetraindoles as agents for the treatment of breast cancer.     

Patients undergoing frozen-thawed embryo transfer have similar live birth rates in spontaneous and artificial cycles

Purpose

To evaluate the outcome of frozen-thawed embryo transfer (FET) when freezing takes place at the pronuclear stage, a retrospective analysis was performed comparing spontaneous and artificial cycles.

Methods

148 women received FET in a spontaneous cycle (Group A) and 55 women received FET in an artificial cycle (Group B) induced by administering estrogen (E2) and progesterone (P). Pregnancy rates, endometrial thickness and serum levels of E2, P and luteinizing hormone (LH) were measured. Statistical analysis included the mean, the standard deviation, the Chi-squared test and the T-test.

Results

The clinical pregnancy rate was 34.5% for Group A and 21.8% for Group B (p = 0.084), with a live birth rate of 20.9% and 12.7% respectively (p = 0.15). There was no difference in endometrial thickness or the P levels, while LH and E2 levels were significantly higher in group B (p < 0.0001).

Conclusion

Our retrospective study shows a trend towards higher pregnancy rates and live birth rates with the administration of FET during a spontaneous cycle compared to FET during an artificial cycle. Large randomized controlled trials are needed to confirm this trend.     

In vivo effects of a SnF2 gel on acid-softened enamel

The purpose of this investigation was to study the intra-oral rehardening of acid-softened enamel and fluoride uptake from SnF2 gel. Bovine enamel slabs were softened with 0.1 mol/L lactate buffer at pH 4.0 for 14 hrs and then mounted in a mandibular removable Hawley appliance. Control slabs were worn for 96 hrs by seven adult males whose teeth were brushed daily with a fluoride-free dentifrice. Test slabs were exposed once/day to 0.4% SnF2 gel. The gel was swabbed onto the slabs for one minute before being replaced in the mouth unrinsed. The natural dentition was brushed 4 X /day with a fluoride-free dentifrice. Microhardness testing was performed after intra-oral exposure (IOE) and after acid-resistance-testing (ART) following immersion in 0.01 mol/L lactate buffer for 24 hrs at pH of 4.0. Fluoride uptake was measured on separate controls, test slabs, and test slabs after ART, with 0.5 mol/L HClO4 etches of from 15 to 60 sec. The F content was measured with a F-ion-specific electrode and the phosphate content by spectrophotometry. Following IOE, microhardness recovery was 35.6% for control and 37.9% for test slabs, and control slabs retained 1.4% resistance to acid, as compared with 18.6% for the test slabs. The F content of control slabs was significantly less than that of SnF2-treated slabs from 5 to 60 micron in depth, and the F content of SnF2-treated slabs after ART was significantly less at depths of from 5 to 35 micron than that of SnF2-treated slabs not exposed to ART. Both control and SnF2 enamel slabs demonstrated rehardening after IOE, but only SnF2-treated enamel retained a significant fraction of that rehardening after ART.     

Langerhans Cells in Dermoid Cysts: Transmission Electron Microscopic, Cytochemical and Immunofluorescent Observations

Langerhans cells were detected in squamous, stratified epithelia lining human dermoid cysts. Their presence was assayed by ATPase staining and reactivity with heteroantisera against "Ia-like" antigens. Transmission electron microscopic studies demonstrated variations in the numbers of cells showing Birbeck granules in epithelia with different degrees of keratinization. Indeterminate cells (i.e. lacking granules), were more frequent in epithelia showing combined mucous and keratinizing differentiation. Membrane-coating-granules and keratohyalin granules were present in epithelia containing Langerhans cells with clearly identifiable Birbeck granules. Interepithelial mast cells were observed in epithelia with mucous differentiation. A relationship between Langerhans cells and keratinization was suggested. Such non-immune functions are compatible with the known macrophage characteristics of the cell.     

Ingesta de calcio y densidad mineral ósea en una población de escolares españoles (estudio CADO)

IntroductionThere are limited data available on bone mass status in Spanish children and or whether the differences are associated with diet/hygiene habits or geographical variability.Subjects and methodsTo determine this association a cross-sectional study was carried out in three different areas (northern, central and southern Spain) and included 1176 schoolchildren between 5 and 12 years old, randomly selected from schools in those areas. Bone density of the distal phalanges was measured by bone ultrasound. We examine the correlations between these data and calcium and vitamin D intake, physical activity and bone mass index.ResultsOf the 1176 children initially included, 1035 nutritional questionnaires were completed and bone ultrasound data were obtained on 991 of them. Eighteen percent of girls and 13% of boys had a calcium intake below 800 mg per day. More than 70% of children have a daily vitamin D intake under 2.5 mcg. Age and exercise showed a direct linear relationship with bone mineral density, and an inverse one for overweight.ConclusionsBoth high physical activity and high calcium intake were associated with a higher bone mineral density, while overweight showed the opposite effect. Diet habits and exercise must be considered the main strategies to prevent adult osteoporosis during childhood.     

Juvenile nasopharyngeal angiofibroma—our experience at a referral hospital

Nasopharyngeal angiofibroma is a rare, highly vascular locally invasive tumor with a strong tendency to bleed. It usually occurs in young adolescent males. This is a retrospective study of 53 patients with nasopharyngeal angiofibroma. All the cases were treated surgically by different conventional approaches depending upon the extent of the mass. Transpalatal approach was used in 32 cases, lateral rhinotomy in 13 cases and a combination of transpalatine + lateral rhinotomy + caldwel-luc in 8 cases. There is no recurrence in 49 cases till date. However, recurrence was noted in four cases within six months. Three out of four patients with recurrence had to undergo repeat surgery for the removal of angiofibroma within six months while the remaining one was referred to radiotherapy as the mass was invading the cavernous sinus. The various clinical presentation and treatment modalities are discussed.