Role of spermatogonia in the stage-synchronization of the seminiferous epithelium in vitamin-A-deficient rats

After 20-day-old rats are placed on a vitamin-A-deficient diet (VAD) for a period of 10 weeks, the seminiferous tubules are found to contain only Sertoli cells and a small number of spermatogonia and spermatocytes. Retinol administration of VAD rats reinitiates spermatogenesis, but a stage-synchronization of the seminiferous epithelium throughout the testis of these rats is observed. In order to determine which cell type is responsible for this synchronization, the germ cell population has been analyzed in whole mounts of seminiferous tubules dissected from the testes of rats submitted to the following treatments. Twenty-day-old rats received a VAD diet for 10 weeks and then were divided into three groups of six rats. In group 1, all animals were sacrificed immediately; in group 2, the rats were injected once with retinol and sacrificed 3 hr later; in group 3, the rats were injected once with retinol, placed on a retinol-containing diet for 7 days and 3 hr, and then sacrificed. Three rats from each group had one testis injected with ³H-thymidine 3 hr (groups 1 and 2) or 7 days and 3 hr (group 3) before sacrifice. Three normal adult rats (approximately 100 days old) served as controls. Labeled and unlabeled germinal cells were mapped and scored in isolated seminiferous tubules. In group 1, type A₁ and type A₀ spermatogonia as well as some preleptotene spermatocytes were present; type A₂ A₃ A₄ In, and B spermatogonia were completely eliminated from the testis. Neither type A₁ mitotic figures nor ³H-thymidine-labeled-type A₁ nuclei were seen. Three hr after retinol injection (group 2), type A₁ mitoses, but no labeled type A₁ nuclei were observed. At 7 days and 3 hr after retinol administration (group 3), type A₄ and In Spermatogonia as well as type A₁ spermatogonia were present. A few residual pachytene spermatocytes were found, and some type A₀ cells were labeled. These results indicate that VAD caused, in addition to an impairment of spermatogenesis at the preleptotene spermatocyte step, a selective momentary arrest of surviving type A₁ spermatogonia at the G₂ phase of their cell cycle. Following administration of vitamin A to VAD rats, these type A₁ cells reinitiated spermatogenesis synchronously and, after several cycless of proliferation and renewai, reconstituted the seminiferous epithelium in a stage-synchronized manner.     

Effects of alpha-adrenoceptor agonists and antagonists on insulin secretion, calcium uptake, and rubidium efflux in mouse pancreatic islets

Epinephrine, norepinephrine or the more selective alpha-2 adrenoceptor agonist, clonidine, inhibited insulin release from isolated pancreatic islets of lean mice or obese mice homozygous for the gene ob. Clonidine was highly effective at 0.1 mumol/l. In contrast, the preferential alpha-1 adrenoceptor agonist, phenylephrine, had no or only a modest effect at 10 mumol/l. The effects of norepinephrine or clonidine were counteracted by yohimbine, a preferential blocker of alpha-2 receptors, but not by prazosine, an alpha-1 receptor blocker. The glucose-stimulated uptake of 45Ca2+ in the islets was only consistently inhibited by epinephrine. This effect was counteracted by yohimbine. Clonidine had no effect on the release of 86Rb+ from preloaded islets. It is concluded that insulin secretion is suppressed by alpha-2 receptor agonism in the pancreatic beta-cells and that this effect is mediated by mechanisms other than the transmembrane fluxes of calcium or potassium ions.     

Nasal mucosal expression of nitric oxide synthases in patients with allergic rhinitis and its relation to asthma.

BACKGROUND: Nitric oxide (NO) has contradictory roles in the pathophysiology of allergic inflammation in both allergic rhinitis (AR) and asthma. Small amounts of NO produced by constitutive NO synthase (NOS) is anti-inflammatory, whereas large amounts produced by inducible NOS (iNOS) are proinflammatory. OBJECTIVE: To investigate the difference in constitutive endothelial NOS (eNOS) and iNOS expression in nonallergic and allergic mucosa and the possible relation of this to the coexistence of asthma in seasonal AR. METHODS: Seventeen patients (10 women and 7 men) with seasonal AR and 9 nonallergic patients (5 women and 4 men) with nasal septum deviation were enrolled. Inferior turbinate nasal biopsy specimens were obtained in all. Levels of eNOS and iNOS expressed as immunohistochemical scores (HSCOREs) were determined immunohistochemically from the specimens. RESULTS: The mean +/- SD HSCOREs for eNOS in patients with seasonal AR were not significantly different from those of the nonallergic controls (1.85 +/- 0.78 vs 1.63 +/- 0.54; P = .12). On the other hand, the mean +/- SD HSCOREs for iNOS were significantly higher in patients with seasonal AR (1.75 +/- 0.75 vs 0.71 +/- 0.6; P = .004). Furthermore, although eNOS expression was not different between seasonal AR patients with and without asthma, the mean +/- SD HSCOREs for iNOS were significantly higher in the patients with asthma (1.93 +/- 0.78 vs 1.65 +/- 0.55; P = .01). CONCLUSION: Increased expression of iNOS might have a role in the development of allergic inflammation in upper and lower airways and in comorbidity of AR and asthma.     

The role of L-carnitine in treatment of a murine model of asthma

Leukotrienes, one of the mediators of inflammation in asthma, have a strong bronchoconstrictive effect. L-carnitine has been reported to influence respiratory functions. It has also been reported that L-carnitine inhibits leukotriene synthesis. To evaluate the effects of L-carnitine on oxygen saturation, urine leukotriene E4 levels and lung histopathology in a murine model of asthma, high IgE responder BALB/c mice (n = 24) were systemically sensitized to ovalbumin and chronically challenged with low particle mass concentrations of aerosolized ovalbumin, and then they were divided into 3 groups (study groups A, B, and C) each including eight mice. After methacholine-induced bronchoconstriction, the mice in groups A and B were given intraperitoneal L-carnitine (250 and 125 mg/kg, respectively), while the mice in group C were given placebo. Oxygen saturation of the mice was measured by pulse oxymeter before and after methacholine and after L-carnitine/ placebo application. In addition, urine leukotriene E4 levels were measured before asthma development, and 24-h after L-carnitine injection in asthmatic mice. Inflammation in the lung tissues of the sacrificed animals was scored histopathologically to determine the effect of L-carnitine on tissue level. A control group of non-sensitized mice (n = 8) treated with placebo only was used for comparison of urine leukotriene E4 levels and of histopathological parameters. Oxygen saturation of the mice in the study groups tended to decrease after methacholine and to improve after L-carnitine injection, although these changes were not significant at all time points. Urine leukotriene E4 levels of all 3 study groups increased significantly after asthma development. The rate of increment was smallest in the group given the highest L-carnitine dose (group A). Inflammation at the tissue level was also mildest in group A, and severest in the group that was not given carnitine (group C). All of the study groups and the control group differed significantly with respect to inflammation scores. In conclusion, L-carnitine improved oxygen saturation, and decreased urine leukotriene E4 levels and inflammation in lung tissues in the present murine model of asthma.     

Dexamethasone treatment attenuates the development of ischaemic brain oedema in gerbils

Transient global forebrain ischaemia was produced in Mongolian gerbils by occluding both common carotid arteries for 10 min followed by 48 h recirculation. Dexamethasone, 5 mg/kg i.p., was given 5 h before the occlusion and every 12 h thereafter. After occlusion an increase in water, sodium and calcium content was found in the parietal cortex and hippocampus, while the concentration of potassium decreased. Exudation of plasma albumin was not found in the brain. The activity of Na+, K(+)-ATPase decreased in the hippocampus. Morphological signs of cerebral oedema were also observed, both in the CA1 region of the hippocampus and in the cortex. Dexamethasone treatment prevented the accumulation of water, sodium and calcium in the ischaemic brain. It also attenuated the oedematous morphological changes of the blood-brain barrier. Thus dexamethasone treatment may also have therapeutic relevance in the acute, high-risk phase of patients suffering from repetitive, transitoric cerebral ischaemia.     

Evidence for the involvement of more than one metal cation in the Schiff base deprotonation process during the photocycle of bacteriorhodopsin

The removal of metal cations inhibits the deprotonation process of the protonated Schiff base during the photocycle of bacteriorhodopsin. To understand the nature of the involvement of these cations, a spectroscopic and kinetic study was carried out on bacteriorhodopsin samples in which the native Ca²⁺ and Mg²⁺ were replaced by Eu³⁺, a luminescent cation. The decay of Eu³⁺ emission in bacteriorhodopsin can be fitted to a minimum of three decay components, which are assigned to Eu³⁺ emission from three different sites. This is supported by the response of the decay components to the presence of ²H₂O and to the changes in the Eu³⁺/bR molar ratio. The number of water molecules coordinated to Eu³⁺ in each site is determined from the change in its emission lifetime when ²H₂O replaces H₂O. Most of the emission originates from two “wet” sites of low crystal-field symmetry—e.g., surface sites. Protonated Schiff base deprotonation has no discernable effect on the emission decay of protein-bound Eu³⁺, suggesting an indirect involvement of metal cations in the deprotonation process. Adding Eu³⁺ to deionized bacteriorhodopsin increases the emission intensity of each Eu³⁺ site linearly, but the extent of the deprotonation (and color) changes sigmoidally. This suggests that if only the emitting Eu³⁺ ions cause the deprotonation and bacteriorhodopsin color change, ions in more than one site must be involved—e.g., by inducing protein conformation changes. The latter could allow deprotonation by the interaction between the protonated Schiff base and a positive field of cations either on the surface or within the protein.     

Therapeutic efficacy and tolerance of diclofensine in psychoreactive depression--a double-blind comparison with placebo

Diclofensine increases the availability of the three neurotransmitters dopamine, noradrenaline and serotonin by inhibiting their re-uptake into synaptosomes. In a randomized double-blind parallel-group comparative study, a total of 40 patients, some hospitalized (n = 11) and some ambulatory (n = 29), mean age of 39.6 years +/- 12 S.D., with psychoreactive depression were treated for 30 days with 2 X 25 mg/day of diclofensine or with placebo. The assessments of efficacy indicated superiority of diclofensine over placebo. The number of "improved" patients (reduction in the overall depression scores by 50% or better) relative to that of "not improved" patients, was found to be statistically significant (p less than 0.025) on day 10 of treatment. With respect to individual symptoms, anxiety showed a significantly (p less than 0.05) better improvement under diclofensine than under placebo. Side effects were observed in one patient in each group. One patient (diclofensine group) reported a transient slight somnolence, the other (placebo group) reported episodes of transient dizziness. Based on these data it can be concluded that diclofensine is a well tolerated and effective drug for the treatment of symptoms associated with reactive depressions.     

Immunomodulatory Effects of Dietary Polyphenols

Functional and nutraceutical foods provide an alternative way to improve immune function to aid in the management of various diseases. Traditionally, many medicinal products have been derived from natural compounds with healing properties. With the development of research into nutraceuticals, it is becoming apparent that many of the beneficial properties of these compounds are at least partly due to the presence of polyphenols. There is evidence that dietary polyphenols can influence dendritic cells, have an immunomodulatory effect on macrophages, increase proliferation of B cells, T cells and suppress Type 1 T helper (Th1), Th2, Th17 and Th9 cells. Polyphenols reduce inflammation by suppressing the pro-inflammatory cytokines in inflammatory bowel disease by inducing Treg cells in the intestine, inhibition of tumor necrosis factor-alpha (TNF-α) and induction of apoptosis, decreasing DNA damage. Polyphenols have a potential role in prevention/treatment of auto-immune diseases like type 1 diabetes, rheumatoid arthritis and multiple sclerosis by regulating signaling pathways, suppressing inflammation and limiting demyelination. In addition, polyphenols cause immunomodulatory effects against allergic reaction and autoimmune disease by inhibition of autoimmune T cell proliferation and downregulation of pro-inflammatory cytokines (interleukin-6 (IL-6), IL-1, interferon-γ (IFN-γ)). Herein, we summarize the immunomodulatory effects of polyphenols and the underlying mechanisms involved in the stimulation of immune responses.