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PubMed1992

Structural implications of spectroscopic characterization of a putative zinc finger peptide from HIV-1 integrase.

The N-terminal domain of human immunodeficiency virus (HIV-1) integrase (IN) contains the sequence motif His-Xaa3-His-Xaa23-Cys-Xaa2-Cys, which is strongly conserved in all retroviral and retrotransposon IN proteins. This structural motif constitutes a putative zinc finger in which a metal ion may be coordinately bound by the His and Cys residues. A recombinant peptide, IN(1-55), composed of the N-terminal 55 amino acids of HIV-1 IN was expressed in Escherichia coli and purified. Utilizing a combination of techniques including UV-visible absorption, circular dichroism, Fourier transform infrared, and fluorescence spectroscopies, we have demonstrated that metal ions (Zn2+, Co2+, and Cd2+) are bound with equimolar stoichiometry by IN(1-55). The liganded peptide assumes a highly ordered structure with increased alpha-helical content and exhibits remarkable thermal stability. UV-visible difference spectra of the peptide-Co2+ complexes directly implicate thiols in metal coordination, and Co2+ d-d transitions in the visible range indicate that Co2+ is tetrahedrally coordinated. Mutant peptides containing conservative substitutions of one of the conserved His or either of the Cys residues displayed no significant Zn(2+)-induced conformational changes as monitored by CD and fluorescence spectra. We conclude that the N terminus of HIV-1 IN contains a metal-binding domain whose structure is stabilized by tetrahedral coordination of metal by histidines 12 and 16 and cysteines 40 and 43. A preliminary structural model for this zinc finger is presented.

Amino Acid Sequence↗
PubMed2005

[Study on D-glucosamine-zn (II) complexes by IR spectral analysis].

In this paper, a series of glucosamine-Zn(II) complexes were synthesized by the reaction of D-glucosamine hydrochloride with ZnSO4 at different pH values. The physical properties and the IR spectra of glucosamine-ZnSO4 complexes were investigated. The absorption at 3346 and 3292 cm(-1) shifted to 3300 cm(-1) due to O--H and N--H stretching, one at 1617 cm(-1) shifted to 1530 cm(-1) due to N-H stretching, and one at 1094 cm(-1) disappeared due to secondary alcohol --OH stretching. But 1033 cm(-1) with primary alcohol --OH did not shift, suggesting that both the amino and secondary hydroxyl groups of glucosamine are coordinated to Zn(II). The results showed that the coordination ability of Zn(II) to glucosamine was enhanced with the pH value increasing, however, the coordination ability weakened when pH value was more than 6.5. So pH 6.5 is an optimal coordination condition for glucosamine-ZnSO4 complexes. The complexes of D-glucosamine with different zinc salts (zinc sulfate, zinc nitrate, zinc acetate, and zinc chloride) were also synthesized at the same pH value, and zinc chloride had weaker coordination ability than other zinc salts. Their IR spectra indicated that glucosamine-Zn(II) complexes with different zinc salts had different coordination model, and only glucosamine-ZnSO4 complex had fixed ratio of coordination under the condition of pH 6.5. The structure of the complex seems to correspond to [Zn(glucosamine)]SO4 7H2O at pH 6.5.

Chlorides↗
PubMedDate not supplied

Advances in the physicochemical, immunologic and cytologic investigation of the synovial fluid.

Investigations of the pathologic synovial fluid (SF), carried out by numerous research teams, have attempted to elucidate certain pathogenic mechanisms suggestive for diagnosis and treatment. Recent studies have tried to draw some biorheologic patterns of the SF, useful for diagnosis and for the evaluation of certain therapies (synoviorthesis). A systematization of the microcrystalline arthropathies has been possible by microscopic examinations of the SF. Enzymologic studies have demonstrated the properties of enzymatic inhibitors of some classical antirheumatic drugs, suggesting the introduction of new antienzymatic products, and have supported the indication for synoviorthesis. Studies of the SF oligoelements have established new criteria for differential diagnosis, have suggested new treatments (by zinc compounds) and have offered explanations for the good effects of some drugs, such as D-penicillamine. Knowing the role of the toxic oxygen radicals in the pathogeny of the rheumatoid synovial inflammation, drugs with a protective action against the effects of free radicals have been introduced in the antirheumatic therapy. Analyses of the various SF cellular populations, including complex immunologic, cytoenzymatic, optic and ultrastructural cytologic investigations, are opening new prospects of clinical application. The general review of the above-mentioned problems is based on the personal experience of the authors and on the latest data in the specialty literature.

Arthritis, Rheumatoid↗
PubMedDate not supplied

[Metabolic efficiency of carbostimulin in therapy of acidosis with diabetes].

The total content of ketoacids, ketonic bodies and state of acid-base balance in blood of sugar diabetes patients was studied as affected by 10-day complex therapy with application of carbostimulin. It is established that carbostimulin lowers the content of ketonic bodies, increases the total content of ketoacids, concentration of buffer bases, CO2, HCO3-. Application of the complex therapy without the preparation causes only a tendency to study the mentioned indexes for the same period of the treatment.

Acid-Base Equilibrium↗
PubMed1995

[Absence of litholytic effects of zinc sulfate and copper sulfate in experimental lithiasis in rats].

Seventy two male Wistar-strain rats were fed lithogenic diet with ethylene-glycol within three weeks. At the end of this treatment, six rats were killed in order to determine the oxalate and calcium concentrations in renal tissue. Remained rats was randomly divided in four series, each series consisting of three groups. In first series (T), the animals were treated with distilled water; in the second (D1Zn), the animals were treated intramuscularly with the zinc at the rate of 24 micrograms per 100 grams of body weight and per day; in the third (D2Zn), 240 micrograms of zinc were administrated to animals and in the last series (D2Cu), the animals were treated at the same dose as the previous series, but with the copper. The groups which making up each series were killed successively at the 5th, 10th and 15th day after ending treatment with ethyleneglycol in order to determine urinary pH, percentage of water in renal tissue, uremia and concentrations of oxalate and calcium in renal tissue. Then, the comparisons of means were carried out, at each time, between different treated groups and reference group which was treated with distilled water. Litholytic effect was found in all series, including that which had been treated with distilled water. However, compared to reference animals, no acceleration of litholytic process was induced by zinc or copper. The high doses used in these experimentations proved therefore that calcium oxalate calculi were insoluble by zinc and copper.

Animals↗
PubMed1994

Methods in pathology. Optimization of proliferating cell nuclear antigen immunohistochemical staining by microwave heating in zinc sulfate solution.

Immunohistochemical staining of routinely processed formalin-fixed, paraffin-embedded archival tissue sections with proliferating cell nuclear antigen (PCNA) monoclonal antibody has facilitated the understanding of the regulation of cell proliferation. However, false-negative staining due to masking or poor preservation of antigen epitopes by fixatives or other unknown conditions has been a major problem in PCNA immunohistochemical studies. Microwave heating (MWH) has been used to retrieve antigen in archival tissue. However, optimal staining conditions have not yet been defined. We therefore investigated the effect of MWH with or without a metal solution (zinc sulfate) on routinely processed paraffin-embedded tissue to determine the optimal conditions for retrieval of PCNA. The results were compared with routine immunohistochemical staining. We found that MWH in 1% zinc sulfate solution successfully retrieved PCNA; the optimal MWH time was 7.5 mins. In contrast, when MWH was performed in water, the specific intensity of PCNA expression was not increased because MWH not only enhanced the intensity of the antigen staining but also increased the background staining. In summary, MWH technique in zinc-sulfate solution allowed successful PCNA retrieval from formalin-fixed archival tissue and thus facilitated accurate immunohistochemical evaluation of cell proliferative activity in cancers.

Antibodies, Monoclonal↗
PubMed1994

Axon-glia interactions regulate ECM patterning in the postnatal rat olfactory bulb.

It has been suggested that an inhibitory ECM containing chondroitin-6-sulfate proteoglycan (C-6S-PG) and tenascin (TN), which appears homogeneously in the core of the OB following afferent fiber arrival, helps position ingrowing olfactory axons in the prospective glomerular layer (GL) (Gonzalez and Silver, 1992; Gonzalez et al., 1993). Later, a similar ECM associated with astrocytes envelopes axonal glomeruli in rings, suggesting that axons may control the precise ECM patterning. The question remains whether formation of the matrix ring pattern around each axonal glomerulus is an intrinsic property of the matrix-producing cells or a response to developing axons. To determine if the organization of glial associated matrix in the OB was dependent on the presence of axons, we studied the effect of unilateral injection of a neurotoxin into the olfactory epithelium of postnatal rats. Using olfactory marker protein (OMP), beta-tubulin (TUJ1) antibodies, and Nissl staining, we found that at 5 and 10 d following neurotoxin administration the number of glomeruli decreased by an average of 77.0% in the injected side. At the same time, we observed that the TN/C-6S-PG rings and periglomerular cells were present only around the remaining small number of glomeruli. Elsewhere, ECM expression and the periglomerular cell configuration were more disorganized in the GL. The pattern of glial fibrillary acidic protein (GFAP) did not change significantly. We found that OMP staining, beta-tubulin immunoreactivity, and periglomerular cells reformed in a glomerular-like pattern as the olfactory axons reformed by 20 d. As the glomeruli-shaped collection of axon terminals reappeared, TN/C-6S-PG immunoreactivity also reoccurred in rings around the new axon bundles. Again, at this later stage, the expression of GFAP was similar in both sides. In our previous study (Gonzalez et al., 1993), we suggested that the initial gross positioning of glomeruli may be controlled by the overall positioning of TN/C-6S-PG. In the present study, we suggest that the formation of TN/C-6S-PG in the precise ring pattern around glomeruli appears to be dependent upon the presence of bundled olfactory axons. Various mechanisms are discussed that may explain the dynamic change in ECM expression that occurs inside the glomerulus after the neurotoxin treatment.

Animals↗
PubMed1995

[Zinc sulfate and heparin for local therapy of herpes. Antiherpetic drugs, not leading to selection of HSV variants].

The massive widespread use of a substance to treat HSV could lead to the spread of resistant HSV strains and hence to a failure of treatment in a vital indication. In Germany, three defined substances suitable for treating HSV are available over the counter: Zinc sulfate, heparin and acyclovir. Experiments show that heparin retains its activity even after 20 passages whereas acyclovir produces a completely resistant virus after only a single passage. The inactivation of free HSV by zinc sulfate is reduced after serial passages. However, this partial resistance disappears again spontaneously and may be considered clinically irrelevant. With respect to drug efficacy and resistance, therefore, a combination of zinc sulfate and heparin would appear superior to zinc sulfate alone. The use of the genotoxic DNA polymerase inhibitor acyclovir should be restricted to severe cases of HSV.

Acyclovir↗
PubMed1995

[Clinical double-blind trial of topical zinc sulfate for herpes labialis recidivans].

In a placebo controlled, double-blind clinical trial in patients with herpes labialis recidivans, zinc sulfate (CAS 7733-02-0) as gel (Virudermin Gel) proved to be significantly more effective than the gel alone. With zinc sulfate as gel, the symptoms were less marked and healing was faster. This simple preparation can be applied in cases of herpes labialis recidivans without any risk of side effects. Due to the antiseptic properties of zinc sulfate superinfections can be prevented.

Administration, Topical↗
PubMed1995

Olfactory marker protein mRNA is found in axons of olfactory receptor neurons.

The separation between the cell bodies of olfactory receptor neurons in the nasal cavity and their axon terminals in the olfactory bulb make them attractive for studying axonal transport. Although high molecular weight RNAs are generally believed to be excluded from axons of mature neurons, we demonstrate here that mRNA for olfactory marker protein (OMP), an abundant cytoplasmic protein selectively expressed in mature receptor cells, is present in rodent olfactory receptor axons. OMP RNA was detected by in situ hybridization at the light microscope level in axons and in terminals. By nuclease protection, the level of OMP RNA in the olfactory bulb was 5-10% of that in the olfactory epithelium where the cell bodies reside. In contrast to axonally transported vasopressin and oxytocin mRNAs, which are deficient in their 3' polyA tails, axonal OMP RNA fractionated as polyA+. OMP RNA was lost from axons and terminals after deafferentation, suggesting that OMP RNA was synthesized in receptor cell bodies in the epithelium and was transported into axons and terminals in the olfactory bulb. RNA for G(olf), a G-protein highly expressed in dendrites of mature olfactory receptor neurons, was not detected in the olfactory bulb. We hypothesize that the immature nature of the cytoskeleton and, specifically, the lack of tightly bundled microtubules allows transport of particular mRNAs in olfactory receptor axons.

Afferent Pathways↗
PubMed1995

[Wilson's disease; diagnosis with the aid of magnetic resonance tomography].

In a 21-year-old woman with a smaller and sloppy handwriting, drooling especially when stooping, sporadic choking, clumsiness, and frequent stumbling, Wilson's disease was diagnosed. The medical history disclosed a short period of haemolytic anaemia with transient hepatic failure, and irregular menstruation periods with infertility. On examination there were no signs of liver or spleen enlargement. She was slow, had an expressionless face and mild dysarthria, and slight impairment of the coordination of the limbs. Magnetic resonance imaging of the brain showed bilateral hyperintensive lesions of the basal ganglia on T2W images. Zinc therapy induced a good biochemical response and there was also some clinical improvement. Linkage analysis within the family identified one other asymptomatic homozygotically affected sister. A diagnostic delay occurs frequently due to relative unfamiliarity with this rare disease and due to its variable clinical expression.

Adult↗
PubMed1995

Comparison of methods for measuring serum immunoglobulin concentrations in neonatal llamas.

Blood samples were collected from 25 neonatal llamas before suckling and at 24, 48, 72, 96, and 120 hours of age. Nine tests for determining serum immunoglobulin concentrations were performed on each sample, to compare within-test variation and correlations among tests. The single radial immunodiffusion assay was the only quantitative test and therefore, was judged the most accurate test for determining the status of passive transfer of immunoglobulins in neonatal llamas. Measurement of globulin concentration and total serum protein, and the sodium sulfite precipitation test were accurate when compared with radial immunodiffusion assay results. Measurements of total serum solids by use of a hand-held refractometer and of albumin concentration, and the zinc sulfate turbidity and 10% glutaraldehyde coagulation tests were not reliable for detecting failure of passive transfer in neonatal llamas. Ten of 25 neonatal llamas were suspected of having partial to complete failure of passive transfer on the basis of results of the single radial immunodiffusion assay. The other tests used in this study identified between 4 and 7 of these 10 llamas at 24 hours of age. On follow-up communication 4 to 6 months after the last-blood sample collection, none of the 25 llamas were identified as having been clinically ill or had received any treatments for illness associated with low immunoglobulin concentrations.

Animals↗
PubMedDate not supplied

[Azoospermia in patients with kidney diseases taking immunosuppressants long term].

Ten sterile males of reproductive age previously treated with immunodepressants were examined andrologically. Azoospermia in them was treated with zinc sulfate (30-90 mg/day, 2-12 months), which was replaced by clomifen citrate in 6 of them (100 mg/day, 2-6.6 months). The response was recorded only in one male: zinc sulfate administration induced subnormal spermatogenesis improved by clomifen citrate as a result of which the patient became a father. In the rest cases azoospermia did not improve. Testicular biopsy performed in 3 patients detected the absence of cells of spermatogenic epithelium (del Castillo syndrome). The absence of response to stimulating therapy may indicate bad prognosis in azoospermia patients with renal diseases treated with immunodepressants.

Adolescent↗
PubMed1994

Zinc salts for the treatment of olfactory and gustatory symptoms in psychiatric patients: a case series.

BACKGROUND: Zinc salts have been used extensively in medical settings to treat disorders of gustatory and olfactory function. However, zinc supplements have not been tested in psychiatric patients with smell or taste symptoms. METHOD: The authors examined the effects of zinc supplements on five consecutive patients with symptoms of abnormal taste and smell perception in the context of acute psychiatric illness or treatment. RESULTS: All five patients had complete or partial amelioration of these olfactory and gustatory symptoms after treatment with zinc sulfate or zinc gluconate, apparently independent of the improvement in their underlying psychiatric disorder. CONCLUSION: We recommend treating unusual olfactory and gustatory symptoms with zinc salts, independent of the treatment for the underlying psychiatric disorder.

Antipsychotic Agents↗