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Direct protection of inosine on PC12 cells against zinc-induced injury.

It has been reported that inosine has no direct neuroprotection against respiratory inhibitors due to the absence of purine nucleoside phosphorylase in neurons. Recent evidence, however, has shown that inosine has direct neurotrophic effects. Thus, lack of direct neuroprotection, as reported before, may not be a general conclusion, but is related to special types of injury. We used PC12 cells to explore direct neuroprotection of inosine against high concentration of zinc sulfate, an injury different from the previous one and found that inosine reduced the mortality of PC12 cells significantly in a dose dependent manner. The results indicate that inosine can directly protect neurons from zinc-induced injury, and such effect might be mediated via mechanism(s) other than purine nucleoside phosphorylase.

Animals↗

The effect of zinc salts on serum bilirubin levels in hyperbilirubinemic rats.

OBJECTIVES: Intestinal metabolism of bilirubin is implicated in the pathogenesis of neonatal jaundice and Crigler-Najjar syndrome. In the present study the authors investigated the effect of oral administration of zinc salts on serum bilirubin levels in hyperbilirubinemic rats. METHODS: Bilirubin-binding activities of zinc sulfate and water-insoluble zinc methacrylate were determined in vitro. Congenitally hyperbilirubinemic Gunn rats and artificially hyperbilirubinemic Wistar rats were used in in vivo studies. Animals were fed a normal diet for 1 week and then a treatment diet of either zinc sulfate or zinc methacrylate for additional 2 weeks. Serum and fecal bile pigments were determined at the end of each phase. Biliary bilirubin secretion rates were determined in hyperbilirubinemic Wistar rats fed zinc methacrylate. RESULTS: Substantial bilirubin-binding activities of zinc salts were demonstrated in in vitro experiments. Treatment with oral zinc salts significantly decreased serum bilirubin levels in Gunn rats (166 +/- 53 versus 123 +/- 38 and 206 +/- 34 versus 131 +/- 31 micromol/L, P < 0.05 for zinc methacrylate and zinc sulfate, respectively). A similar effect of zinc methacrylate was also observed in hyperbilirubinemic Wistar rats (102 +/- 10 versus 14 +/- 4 micromol/L, P < 0.0001). In accord, biliary bilirubin secretion decreased significantly in these animals (45 +/- 11 versus 28 +/- 4 nmol/h 100g body weight, P < 0.02). In contrast to zinc sulfate, treatment with zinc methacrylate did not lead to the elevation of serum zinc levels. CONCLUSIONS: Oral administration of zinc salts efficiently decreased serum bilirubin levels in hyperbilirubinemic rats, presumably as a result of inhibition of enterohepatic circulation of bilirubin. This approach might be useful in the treatment of severe unconjugated hyperbilirubinemias.

Administration, Oral↗

Anti-growth effects with components of Sho-saiko-to (TJ-9) on cultured human hepatoma cells.

The present study was undertaken to investigate the effects and the mechanism of the components of Sho-saiko-to (baicalein, baicalin, saikosaponin-a, saikosaponin-c, ginsenoside Rb1, ginsenoside Rg1) on cultured human hepatoma cells (HuH-7). Cell cycle analysis was carried out with flow cytometry and the bromodeoxyuridine (BrdU)-labelling method. The results showed that baicalein, baicalin and saikosaponin-a inhibited cell proliferation dose-dependently but independently of the cell cycle. Furthermore, it was found that saikosaponin-a possesses a strong cell-killing effect. On the other hand, saikosaponin-c, ginsenoside Rb1 and ginsenoside Rg1 had no effect on cell proliferation.

Antineoplastic Agents↗

Cytoprotective effect of gallotannin in oxidatively stressed HaCaT keratinocytes: the role of poly(ADP-ribose) metabolism.

Oxidative stress-induced cytotoxicity is mediated in part by accelerated poly-ADP ribosylation. Peroxynitrite and hydrogen peroxide cause DNA breakage triggering the activation of the DNA nick sensor enzyme poly(ADP-ribose) polymerase-1 (PARP-1). Overactivation of PARP-1 leads to cell dysfunction and cell death mainly due to depletion of NAD(+) (the substrate of PARP-1) and ATP. PARP-1 attaches most ADP-ribose residues onto itself, leading to downregulation of enzyme activity. Here, we have investigated the role of poly(ADP-ribose) glycohydrolase (PARG), the poly(ADP-ribose)-catabolyzing enzyme in oxidative stress-induced cytotoxicity in HaCaT cells. We have found that inhibition of PARG by gallotannin (GT) (50 microM) provided significant cytoprotection to peroxynitrite- or hydrogen peroxide-treated HaCaT cells, as assessed by lactate dehydrogenase release and propidium iodide uptake (parameters of necrotic cell death) as well as caspase activation (apoptotic parameter). GT pretreatment has also inhibited the depletion of cellular NAD(+) pools in hydrogen peroxide- or peroxynitrite-treated HaCaT cells. GT caused the accumulation of poly(ADP-ribose) and concomitant inhibition in cellular PARP activity in oxidatively stressed cells. Therefore, PARG is likely to contribute to maintaining the active state of PARP-1 by continuously removing inhibitory ADP-ribose residues from PARP-1.

Astringents↗

Effects of topically-applied antiperspirant on sweat gland function.

In subjects exposed to a hot environment, short-term topical pretreatment with aluminium zirconium tetrachlorhydrate delayed the onset of visible sweating although it failed to prevent the response. The delay was considered most probably to be due to the occlusive action, in the duct within the upper epidermis, of aluminium-containing conglomerates, which disappear after continuous sweating. However, microanalytical evidence indicated that ionic transport within the fundus secretory cells was also modified.

Administration, Topical↗

Aluminum chloride hexahydrate versus palmar hyperhidrosis. Evaporimeter assessment.

The efficacy of topical aluminium chloride hexahydrate 20% W/W ethanol (ACH) in the treatment symptomatic palmar hyperhidrosis was studied in 12 patients. A half-sided control single blind (assessor blind) study was done. Patients applied ACH on one palm daily for 4 weeks. The response to treatment was measured objectively with an evaporimeter. There was significant fall of skin water vapor loss (SVL) on treated palms compared with untreated palms. The basal mean SVL of treated palms and untreated palms were 79.9 and 77.9 g water/m2/h, respectively (n.s.). The mean SVLs of treated vs. untreated palms at week 1, 2, 3, and 4 were 66.4 vs. 79.7 (p less than 0.05), 56.6 vs. 72.2 (p less than 0.001), 58.2 vs. 72.5 (p = 0.1), and 51.4 vs. 72.7 (p less than 0.001) g water/m2/h, respectively. The mean SVL of treated palms returned near basal rate within 1 week of stopping treatment. Four patients developed skin irritation from ACH; in three this disappeared after 1 week and they were able to continue with treatment; one withdrew from the study because of the severe irritation. All patients reported that the ACH reduced palmar sweating within 48 hours of application; its effect disappeared within 48 hours after stopping treatment. ACH appeared to be useful in rapid control of palmar hyperhydrosis.

Administration, Cutaneous↗

Oral zinc sulfate in the treatment of rosacea: a double-blind, placebo-controlled study.

BACKGROUND: Rosacea is a skin problem not uncommonly encountered world-wide. There is a need for an effective and well-tolerated treatment for this disease. OBJECTIVE: To evaluate the efficacy and side-effects of zinc sulfate in rosacea in a randomized, controlled, double-blind trial. PATIENTS AND METHODS: Patients with rosacea who attended the outpatient Clinic of Dermatology and Venereology in Baghdad Teaching Hospital were recruited into this study between October 2002 and August 2004. A disease severity score was calculated for each patient. The patients were randomly allocated to receive either zinc sulfate 100 mg or identical placebo capsules three times per day. Zinc sulfate and placebo capsules were given in a double-blind manner. Following 3 months of starting the treatment, the patients crossed over, i.e. patients on placebo crossed over to zinc sulfate and those on zinc sulfate crossed over to placebo. RESULTS: Twenty-five patients with rosacea were included in this study: 16 (64%) females and nine (36%) males. Nineteen patients completed the study: 11 (58%) females and eight (42%) males. Patient age ranged from 21 to 64 years with a mean +/- SD of 48.2 +/- 9.3 years. Duration of the disease ranged from 1 to 14 years with a mean +/- SD of 4.4 +/- 3.2 years. In the group started on zinc sulfate, the score before therapy ranged from 5 to 11 with a mean +/- SD of 8 +/- 2.0. The mean started to decrease directly after the first month of therapy with zinc sulfate to a significantly lower level. After shifting to placebo treatment, the mean started to rise gradually in the fifth month but remained significantly lower than the levels before therapy. In the group started on placebo, the score before therapy ranged from 5 to 9 with a mean +/- SD of 7 +/- 1.3. The mean remained high in the first 3 months of therapy while the patients were on placebo. After shifting to zinc sulfate, the mean started to decrease after the fourth month to significantly low levels. No important side-effects were reported apart from mild gastric upset in three (12%) patients on zinc sulfate. CONCLUSION: Zinc sulfate was found to be a good option in the treatment of rosacea, as it was safe, effective and lacking important side-effects.

Administration, Oral↗

Changes in reelin expression in the mouse olfactory bulb after chemical lesion to the olfactory epithelium.

To explore the functional roles of Reelin in the adult olfactory system, we examined changes in the expression of reelin mRNA and Reelin protein in the olfactory bulb (OB) of adult mice after a chemical lesion to the olfactory epithelium. Following intranasal irrigation with 2% zinc sulphate solution, animals were perfused at various times between 5 and 40 days post-lesion. The expression of reelin mRNA in mitral cells in the OB was slightly reduced at 5 days post-lesion, completely abolished by 20 days, but restored almost to the normal level at 40 days post-lesion. Similarly, the expression of Reelin protein in mitral cells of the deafferented OB also recovered, although not to the normal level. No recovery of either reelin mRNA or Reelin immunoreactivity was seen in the periglomerular cells and external tufted cells. The expression profile of reelin mRNA and Reelin protein in the OB coincided with the time course of degeneration and regeneration of olfactory nerves, as indicated by anterograde labeling of olfactory nerves with WGA-HRP. These results suggest that expression of reelin mRNA in the adult OB is regulated by olfactory inputs.

Animals↗

Aluminum posttranscriptional regulation of parathyroid hormone synthesis: a role for the calcium-sensing receptor.

BACKGROUND: Calcium regulates parathyroid hormone (PTH) gene expression by a posttranscriptional mechanism, as well as parathyroid gland growth through the activation of the calcium-sensing receptor. Aluminum decreases both parathyroid cell proliferation and PTH levels by an unknown mechanism. METHODS: To investigate the possible role of calcium-sensing receptor in the aluminum-induced PTH inhibition we used human embryonic kidney (HEK-293) cells transiently transfected with the human calcium-sensing receptor. We used a parathyroid gland tissue culture model to investigate whether the effect of aluminum in PTH mRNA was a transcriptional mechanism and also its possible role in calcium-sensing receptor expression. RESULTS: We found that Al activated the calcium-sensing receptor with higher efficiency than calcium, its biologic ligand. Aluminum inhibited PTH gene expression by a posttranscriptional mechanism, but only when low calcium is present in the medium. Finally, we found that aluminum is also able to decrease calcium-sensing receptor mRNA levels by a posttranscriptional mechanism; however, no effect was observed on calcium-sensing receptor protein. CONCLUSION: These findings indicate that aluminum impairs parathyroid function through a calcium-like mechanism due to the lack of specificity of the calcium-sensing receptor. Additionally, aluminum decreases parathyroid calcium-sensing receptor mRNA levels, and the regulatory mechanism was posttranscriptional. These findings demonstrate for the first time a regulatory effect in the calcium-sensing receptor by one of its ligands.

Aluminum Chloride↗

Comparison of topical therapy for striae alba (20% glycolic acid/0.05% tretinoin versus 20% glycolic acid/10% L-ascorbic acid).

BACKGROUND: Topical treatment of striae rubra with 0.1% tretinoin and laser treatment of striae rubra and alba with the 585-nm pulsed dye laser are proven therapeutic options. However, little efficacy has been shown for treatment of striae alba topically, and the laser is currently not a suitable treatment option for darker ethnic skin types. OBJECTIVE: The purpose of this study was to demonstrate that selected commercial topical agents can improve the appearance of striae alba. METHODS: Ten patients of varying skin types (I-V) having straie distensae alba on the abdomen or thighs were selected to evaluate the effectiveness of two topical treatment regimens. Patients were placed on daily topical application of 20% glycolic acid (MD Forte) to the entire treatment area. In addition, the patients applied 10% L-ascorbic acid, 2% zinc sulfate, and 0.5% tyrosine to half to the treatment area and 0.05% tretinoin emollient cream (Renova) to the other half of the treatment area. The creams were applied on a daily basis for 12 weeks. Improvement was evaluated at 4 and 12 weeks in an objective unblinded fashion at the follow-up visits, a objective blinded fashion by visual grading at the conclusion of the study, and in an objective blinded fashion with profilometry. Additionally, histopathologic analysis was performed. RESULTS: Analysis of these data reveals: 1) both regimens can improve the appearance of stretch marks; 2) these topical therapy regimens are safe and effective in study patients with minimal irritation; 3) elastin content within the reticular and papillary dermis can increase with topical 20% glycolic acid combined with 0.05% tretinoin emollient cream therapy; 4) both regimens increased epidermal thickness and decreased papillary dermal thickness in treated stretch marks when compared with untreated stretch marks; 5) combined epidermal and papillary dermal thickness in stretch marks treated with either topical regimen approaches that of normal skin; and 6) profilometry can objectively measure differences in skin texture associated with striae treatments when compared to controls, however, it is not sensitive enough to justify comparison or quantitative improvements between similarly effective treatments.

Abdomen↗

Current methods of finish-line exposure by practicing prosthodontists.

PURPOSE: The purpose of this study was to survey members of The American College of Prosthodontists to evaluate current methods of finish-line exposure. In addition, frequency of use of epinephrine compounds and observed side effects were assessed. MATERIALS AND METHODS: A questionnaire was mailed to the 2,436 members of The American College of Prosthodontists. Group differences were evaluated using chi 2 analysis. RESULTS: Completed questionnaires were returned by 1,246 prosthodontists, which is a return rate of 51%. Ninety-eight percent of respondent prosthodontists use retraction cord, and 48% use a double-cord technique. Plain cord is the most commonly used cord (44%), followed by aluminum chloride-impregnated cord (18%), and epinephrine-impregnated cord (14%). Nine hundred one respondents (81%) soak the cord before placing it in the gingival sulcus. The most common medicament for soaking the cords is buffered aluminum chloride (55%). Side effects to epinephrine were reported by 387 respondents (33%), with the most common side effect reported being increased pulse rate, followed by anxiety. Approximately one quarter (24%) of the prosthodontists surveyed had observed side effects to chemical agents other than epinephrine. CONCLUSIONS: Prosthodontists throughout the country use many different techniques and agents to expose finish lines. No statistically significant differences (p > .05) were found between year of specialty training completion groups with respect to retraction cord use. Copper bands are used significantly more frequently (p < .05) in the northwest region of the United States than elsewhere.

Aluminum Chloride↗