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Percutaneous absorption of DDT from a parasiticide used for treatment of scabies.

Moderately to markedly increased plasma concentrations of DDT and its major metabolite DDE were found in 3 boys 4, 7 and 9 years of age and also in a 50-year-old woman who, because of suspected or proven scabies infection, had all repeatedly received between 7 and 200 applications of Tenutex (a DDT-containing scabicide) during recent years. Normal values were found in 4 untreated children and in 2 children who had been treated with Tenutex four and three times respectively. In 9 adults there was no significant increase in the plasma concentrations of DDT and DDE after a single 24-hour treatment with Tenutex. These results indicate that DDT, a known constituent of the scabicide Tenutex, can be percutaneously absorbed and lead to measurably increased plasma concentrations after repeated application, especially in children.

Administration, Topical↗

Treatment of canine scabies with milbemycin oxime.

The purpose of this study was to determine the efficacy of orally administered milbemycin oxime in the treatment of canine scabies. Forty dogs were treated. Mean drug dosage for all dogs was approximately 2 mg/kg body weight. Twenty-seven dogs received 3 doses separated by 7 d, and 13 dogs received 2 doses separated by 14 d. All dogs were clinically normal following treatment and no adverse reactions were detected.

Administration, Oral↗

Topical (pour-on) ivermectin in the treatment of canine scabies.

The efficacy of a pour-on formulation of ivermectin at 500 micrograms/kg body weight applied on the dorsum on days 1 and 15 was evaluated in 90 dogs from a shelter, naturally infested with Sarcoptes scabiei. This very practical form of treatment was successful in eradicating scabies from this shelter.

Administration, Topical↗

Secondary bacterial infection in Ghanaian patients with scabies.

From 110 patients with secondarily infected scabies lesions, 105 bacteria consisting of 66 aerobes and 39 anaerobes were isolated. A mixture of aerobic and anaerobic bacteria was present in 15 (13.6%). The predominant aerobic and anaerobic bacteria were staphylococcous aureus 39.1% and pepostreptococcus spp. 14.2% respectively. Organisms that resided in the mucus membranes close to or in contact with the lesions predominated in those infections. Most organisms were recovered from the finger and buttock lesions. These organisms were mainly staph. aureus, beta-haemolytic streptococci group. A and peptostreptococcus. More than 80% of staph. aureus isolated were resistant to penicillin. Less than 20% of the anaerobes were resistant to penicillin. The enteric Gram-negative, E. coli and Klebsiella spp. showed 100% sensitivity to Amoxycilin/clavulanic acid and gentamicin. Pseudomonas spp. were only susceptible to gentamicin, Amoxycillin/clavulanic acid proved to be the most active therapeutic agent in in vitro against the isolated microorganisms.

Bacteria, Aerobic↗

[Re-emergence of Norwegian scabies in our environment].

It is reported this uncommon variety of scabies in Cuban patients that caused an epidemic in its areas of origin. It is stressed the severe prutitus observed among these patients, which is usually mild or is absent. It is recommended the dermatological isolation of these individuals and the adoption of prophylactic measures for the personnel being in direct contact with them.

Acquired Immunodeficiency Syndrome↗

[Treatment of drug resistant scabies].

Thirty patients suffering from scabies who had previonsly received other kinds of treatment were administered "Metrifonate" at daily doses of 10 mg./kg. b.w. during two consecutive days repeated every week and associated with atropine sulfate. The number of weeks lapse until the treatment finished was as follows. (see article.) Four patients developed intolerance, but it was transitory (nausea and vomiting). Cures (skin lesions and prutitus) were obtaind in 29 our of 30 cases.

Adolescent↗

The relation between scabies and hypersensitivity to antigens of house dust mites and storage mites.

Twenty five non-atopic scabietic patients were examined to estimate their reaction to crude house dust mite Dermatophagoides farinae (D. farinae) and storage mite Tyrophagus putrescentia (T. putrescentiae) antigens. Skin prick testing (SPT) by extracts of both mites antigens showed significant higher positive results in scabietics when compared to non-scabietic control subjects. Moreover, 60% and 56% of scabietic patients showed positive levels of specific anti-D. farinae and T. putrescentia IgE respectively in comparison to 13.4% & 20% of control subjects. A significant difference has been obtained when the total number of positive results were compared to the total number of negative ones. The results revealed that there is an evidence of cross reactivity between Sarcoptes scabiei antigens and extracts of D. farinae and T. putrescentiae, and the hypersensitivity to house dust mite and storage mite antigens was significantly higher in scabietics than in controls. It could be concluded that there is some proof that other mites rather than Sarcoptes scabiei may have a role in the pathogenesis of scabies and the cross reactivity between S. scabiei and house dust mite and storage mite may explain the persistence of symptoms in some cases even after proper treatment of the disease.

Adolescent↗

Isolation and characterization of two types of actinophage infecting Streptomyces scabies.

Two types of actinophages, phi S and phi L, were isolated from soil samples by using Streptomyces scabies, a potato scab pathogen, as indicator strain. The phages were partially characterized according to their physicochemical properties, plaques and particles morphology, and their host range; this varied from narrow (for phi S) to wide (for phi L). The adsorption rate constants of the phi S and phi L were 3.44 and 3.18 pL/min, and their burst sizes were 1.61 and 3.75 virions per mL, respectively. One-step growth indicated that phi S and phi L have a latent period of 1/2 h followed by a rise period of 1/2 h. The temperate character of these phages was tested in other isolates of Streptomyces. Four of the phages (phi SS3, phi SS12, phi SS13 and phi SS17) were identified as temperate phages, since they were able to lysogenize SS3, SS12, SS13 and SS17. phi SS3, phi SS12 and phi SS13 were homoimmune, and they were heteroimmune with respect to phi SS17. The restriction barriers of lysogenic isolates (SS12, SS13 and SS17) interfered with the blockage of plaque formation by phages (phi SS12, phi SS13 or phi SS17) propagated on them, about 75% of lysogenic isolates had restriction systems. The exposure of the lysogenic isolates (SS12, SS13 and SS17) to UV-irradiation prevented the possible restriction barriers of these isolates so that these barriers could be overcome.

Bacteriophages↗

Mutational analysis of the Streptomyces scabies esterase signal peptide.

Ten site-directed mutations affecting the predicted 39-amino-acid signal peptide of the Streptomyces scabies esterase were used to examine start-codon usage and esterase secretion in S. lividans. The first of two in-frame AUG codons was preferred for translation initiation. Removal of 2 of the 4 positively charged amino acids at the amino terminus of the signal peptide reduced esterase expression more than 100-fold; however, deletion of all 4 charged residues reduced expression by only 2- to 5-fold. Deletion of 4 or 8 amino acids from the hydrophobic core of the signal peptide reduced esterase production more than 200-fold, and a signal peptide processing site deletion completely disrupted esterase expression. For all constructs in which a mutation in the signal sequence decreased esterase production, esterase mRNA levels were also reduced, suggesting that a defect in secretion or processing affected esterase transcript abundance.

Amino Acid Sequence↗

Crystallization and preliminary crystallographic data of a Streptomyces scabies extracellular esterase.

X-ray quality single crystals of an extracellular esterase from pathogenic Streptomyces scabies were obtained by the hanging drop method. The crystals are monoclinic (space group C2, a = 161.1 A, b = 51.2 A, c = 124.2 A, beta = 100.6 degrees) with two molecules related by a noncrystallographic dyad in the asymmetric unit, with a solvent content of approximately 64%. The diffraction pattern from fresh crystals extends beyond 2 A resolution using sealed tube CuK alpha radiation. The study has been initiated in order to elucidate the mechanism of this unusual non-serine-dependent esterase, and to gain better understanding of the molecular basis of the pathogenesis of the scab disease.

Crystallization↗

Cloning and sequencing of a secY homolog from Streptomyces scabies.

The complete DNA sequence of the Streptomyces scabies (Ss) secY homolog and partial sequences of adjacent upstream and downstream open reading frames (ORFs) have been determined. The nucleotide sequence of a 2-kb region predicts a polypeptide of 437 amino acids in length with homology to the SecY protein family. The Ss secY homolog lies upstream from a sequence that has homology to the adenylate kinase gene (adk) family. The translational stop codon of the putative SecY ORF overlaps the predicted start codon for the Adk ORF. Another ORF that lies upstream from the secY homolog has sequence similarity to the genes that code for the L15 r-protein. Within the 243-bp intergenic region between the L15 and SecY coding sequences, the presence of a streptomycete-like promoter sequence and an 18-bp inverted repeat suggests that the secY homolog and the adjacent downstream sequences may be transcribed independently of the L15 coding sequence. Transcript analysis indicates that the secY homolog is expressed in both Ss and Streptomyces lividans. The proposed gene and transcript organization of the L15-SecY-Adk coding regions in the Ss clone resembles that of Micrococcus luteus which, like the streptomycetes, has a G+C-rich genome.

Adenylate Kinase↗

Effect of some organic phosphorus and carbamate pesticides on Streptomyces scabies.

Of all the organic phosphorus and carbamate pesticides, tested on Streptomyces scabies, Thimet, Chlorothion, Dithane M-45, and Karathane, were effective at relatively low concentrations (1, 20, 16, and 115 ppm). Minimal inhibitory concentrations of these pesticides were the same in vitro as well as in vivo. The other organic phosphorus and carbamate compounds tested were less effective under the laboratory conditions of these tests.

Carbamates↗

A novel variant of the catalytic triad in the Streptomyces scabies esterase.

The crystal structure of a novel esterase from Streptomyces scabies, a causal agent of the potato scab disease, was solved at 2.1 A resolution. The tertiary fold of the enzyme is substantially different from that of the alpha/beta hydrolase family and unique among all known hydrolases. The active site contains a dyad of Ser 14 and His 283, closely resembling two of the three components of typical Ser-His-Asp(Glu) triads from other serine hydrolases. Proper orientation of the active site imidazol is maintained by a hydrogen bond between the N delta-H group and a main chain oxygen. Thus, the enzyme constitutes the first known natural variation of the chymotrypsin-like triad in which a carboxylic acid is replaced by a neutral hydrogen-bond acceptor.

Amino Acid Sequence↗

Purification and characterization of a novel extracellular esterase from pathogenic Streptomyces scabies that is inducible by zinc.

Native polyacrylamide gels of extracellular proteins produced by several Streptomyces isolates grown with suberin were assayed in situ for esterase activity. Two pathogenic isolates of Streptomyces scabies from different geographical regions were found to produce a similar esterase activity that was not produced by nonpathogenic strains. After treatment with EDTA, suberin no longer induced esterase production. Expression was restored when EDTA-treated suberin was supplemented with zinc. The optimal concentration of zinc required for esterase production was 2 microM. This esterase was purified from one of the pathogenic isolates and characterized. The enzyme was 38,000 daltons when determined by gel filtration on Sephadex G-100 and 36,000 daltons when determined by denaturing polyacrylamide gel electrophoresis. The esterase showed maximal activity in sodium phosphate buffer above pH 8.0, was stable to temperatures of up to 60 degrees C, and had an apparent Km of 125 microM p-nitrophenyl butyrate.

Enzyme Induction↗

Cloning, sequencing, and regulation of expression of an extracellular esterase gene from the plant pathogen Streptomyces scabies.

The gene that encodes the extracellular esterase produced by Streptomyces scabies has been cloned and sequenced. The gene was identified by hybridization to a synthetic oligonucleotide that corresponds to the amino-terminal amino acid sequence determined for the secreted form of the esterase. Nucleotide sequence analysis predicted a 345-amino-acid open reading frame, a putative ribosome-binding site, and 39 amino acids at the amino terminus of the sequence that is not found in the secreted protein. This 39-amino-acid sequence has many of the characteristics common to known signal peptides. End mapping the esterase transcript revealed a single 5' end of the mRNA located 51 nucleotides upstream from the start point for translation. Northern (RNA) hybridization analysis of the esterase message by using the cloned esterase gene as a probe indicated that the esterase mRNA is about 1,440 nucleotides in length and was detected only when the cells were grown in the presence of zinc. These results suggest that the level of esterase mRNA detected in the cells is regulated by zinc.

Base Sequence↗

Hematology in the regressive phase of bovine psoroptic scabies.

Hereford calves were infested with Psoroptes ovis. Hemograms were evaluated weekly for 7 weeks during progressively extensive dermatitis and compared to uninfested control calves. Calves were treated with ivermectin and weekly hemograms were compared for 4 weeks during regression of clinical disease. They developed extensive dermatitis and marked decreases in total white blood cells, neutrophils, and lymphocytes. Infested calves also had moderate anemia, increased plasma proteins, and increased plasma fibrinogen. Some calves developed marked eosinophilia. Within 1 week after ivermectin treatment, nearly all hematologic parameters returned or began to return to normal values, even though scabs remained on the calves at 4 weeks. Peak eosinophilia in calves which responded occurred 1 to 2 weeks after treatment. The findings indicate that most of the hematologic changes occurring with psoroptic scabies in cattle are associated with living mites and not with toxic substances in the scab on the skin surface.

Animals↗

Isolation and characterization of two types of actinophages infecting Streptomyces scabies MR13.

Two types of actinophages, phi S and phi L, were isolated from soil samples by using Streptomyces scabies MR13, a potato scab pathogen, as an indicator strain. The phages were partially characterized according to their physicochemical properties, plaques and particles morphology and their host-range. The host-range of these phages was narrow for phi S and wide for phi L. The adsorption rate constants of the phi S and phi L were 3.44 x 10(-9) and 3.18 x 10(-9) ml/min, and their burst sizes were 1.61 and 3.75 virions, respectively. One-step growth indicated that phi S and phi L have a latent period of 30 min followed by a rise period of 30 min. The temperate character of these phages was tested in other isolates of Streptomyces. Four of the phages (phi SS3, phi SS12, phi SS13 and phi SS17) were identified as temperate phages, since they were able to lysogenize SS3, SS12, SS13 and SS17. phi SS3, phi SS12 and phi SS13 were homoimmune, and they were heteroimmune with respect to phi SS17. The restriction barriers of lysogenic isolates (SS12, SS13 and SS17) interfered with the blockage of plaques formation by phages (phi SS12, phi SS13 or phi SS17) propagated on them, about 75% of lysogenic isolates had restriction systems. The exposure of the lysogenic isolates (SS12, SS13 and SS17) to UV-irradiation prevented the possible restriction barriers of these isolates, and these barriers could be overcome.

Bacteriophages↗

Extracts of scabies mites (Sarcoptidae: Sarcoptes scabiei) modulate cytokine expression by human peripheral blood mononuclear cells and dendritic cells.

We performed a series of experiments to determine if human peripheral blood mononuclear cells (PBMCs) from a healthy donor and dendritic cells (NHDCs) derived from these PBMCs reacted to molecules in a scabies extract. PBMCs extravasate from the circulatory system and enter tissues such as scabietic lesions, where monocytes become macrophages. Cells were cultured in medium alone or medium containing 50 microg/ml of Sarcoptes scabiei (SS) extract, 50 ng/ml E. coli lipopolysaccharide (LPS), or SS + LPS together. Supernatants were collected and assayed by enzyme-linked immunosorbent assay (ELISA) for specific cytokines. PBMCs stimulated with SS or LPS exhibited moderately upregulated production of interleukin (IL)-1beta and huge increases in secretions of IL-6, IL-8 and TNF-alpha. Cells co-stimulated with both SS and LPS generally secreted more of these cytokines than cells stimulated with either SS or LPS alone. LPS induced a small amount of IL-1alpha secretion, whereas SS did not, and neither additive resulted in the production of IL-10. NHDCs did not produce IL-1alpha, IL-1beta, IL-6, IL-8, or IL-10 in response to stimulation with SS. These cells did produce IL-6, IL-8, and tumor necrosis factor (TNF)-alpha in response to LPS. When cells were co-stimulated with both LPS and SS, the production of IL-6 and IL-8 was significantly reduced compared with the levels secreted after LPS stimulation alone. These studies show that molecules in a whole body extract of S. scabiei modulate the function of PBMCs (probably monocytes) and dendritic cells.

Animals↗