Signs Of Photosensitivity Research Articles

Mutation responsible for congenital photosensitivity and hyperbilirubinemia in Southdown sheep.

OBJECTIVE To identify the genetic cause for congenital photosensitivity and hyperbilirubinemia (CPH) in Southdown sheep. ANIMALS 73 Southdown sheep from a CPH research flock and 48 sheep of various breeds from commercial flocks without CPH. PROCEDURES Whole-genome sequencing was performed for a phenotypically normal Southdown sheep heterozygous for CPH. Heterozygous variants within Slco1b3 coding exons were identified, and exons that contained candidate mutations were amplified by PCR assay methods for Sanger sequencing. Blood samples from the other 72 Southdown sheep of the CPH research flock were used to determine plasma direct and indirect bilirubin concentrations. Southdown sheep with a plasma total bilirubin concentration < 0.3 mg/dL were classified as controls, and those with a total bilirubin concentration ≥ 0.3 mg/dL and signs of photosensitivity were classified as mutants. Sanger sequencing was used to determine the Slco1b3 genotype for all sheep. Genotypes were compared between mutants and controls of the CPH research flock and among all sheep. Protein homology was measured across 8 species to detect evolutionary conservation of Slco1b. RESULTS A nonsynonymous mutation at ovine Chr3:193,691,195, which generated a glycine-to-arginine amino acid change within the predicted Slco1b3 protein, was significantly associated with hyperbilirubinemia and predicted to be deleterious. That amino acid was conserved across 7 other mammalian species. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested a nonsynonymous mutation in Slco1b3 causes CPH in Southdown sheep. This disease appears to be similar to Rotor syndrome in humans. Sheep with CPH might be useful animals for Rotor syndrome research.

Transient erythropoietic protoporphyria associated with chronic hepatitis and cirrhosis in a cohort of German shepherd dogs

Over the course of one year, slight jaundice and ascites suggestive of chronic liver disease occurred in 17 German shepherd dogs from one breeding colony. Blood analyses, performed twice with...

Kindler syndrome in a Saudi kindred.

We report a large consanguineous Saudi-Arabian pedigree containing 11 individuals with the autosomal recessive genodermatosis, Kindler syndrome. Three affected cases died in infancy but the remaining eight had signs of photosensitivity, generalized poikiloderma, webbed fingers, loss of dermatoglyphics and nail dystrophy. The majority also had oral involvement with bleeding gums. Additional features seen in some cases included pseudoainhum of the toes, sclerotic bands on the wrists and hand deformities. The aetiology of Kindler syndrome is not yet known, but the underlying defect leads to both cutaneous and oral inflammation, along with photosensitivity and scarring.

Urinary porphyrin excretion in hepatitis C infection.

A high prevalence of hepatitis C virus infection in porphyria cutanea tarda in some populations suggests a close link between viral hepatitis and alteration of porphyrin metabolism. Moreover, there is evidence of a role of porphyrinopathies in hepatocarcinogenesis. The aim of our study was to obtain data on the prevalence and patterns of heme metabolism alterations in patients with chronic hepatitis C virus infection. Urinary porphyrin excretion was prospectively studied in 100 consecutive outpatients with chronic hepatitis C infection without signs of photosensitivity, using an ion-pair high-performance liquid chromatography method. Increased total porphyrin excretion was found in 41 patients, with predominant excretion of coproporphyrins (whole study group: mean 146 microg/g creatinine, interquartile range 76-186; normal < 150), in 10 patients excretion exceeded 300 microg/g creatinine. In the majority of all patients studied (75/100) an increased ratio of the relatively hydrophobic coproporphyrin isomer I to isomer III was found. In just one case, urinary porphyrin pattern characteristic for chronic hepatic porphyria was present (uroporphyrin > coproporphyrin, heptacarboxyporphyrin III increased) but the total porphyrin excretion was only slightly elevated in this case. In the whole group, total urinary porphyrin excretion correlated well with serum bilirubin and was inversely correlated with albumin and thrombin time. In conclusion, secondary coproporphyrinuria occurs frequently in heptatitis C infection, whereas in Germany, preclinical porphyria cutanea tarda seems to be rare in these patients.

Photosensitization in Lambs Grazing Switchgrass

AbstractHepatogenous photosensitization has been recorded in herbivores grazing a number of Panicum species in different areas of the world. This condition was observed in weaned and suckling lambs (Ovis sp.) grazing switchgrass (Panicum virgatum L. cv. Cave‐in‐Rock) in Morgantown, WV, during the abnormally hot, dry summer of 1991. The first cases occurred in June, 35 d after initiation of grazing. Further cases occurred with a new group of lambs 12 d after their introduction to switchgrass pastures in late July. Of a total of 104 lambs, 17 showed photosensitization and eight died. Symptoms were similar to those reported for ‘geeldikkop’ in sheep and hepatotoxicity was confirmed by changes in blood metabolites. Mature ewes were not affected and no signs of photosensitization were noted in suckling lambs grazing switchgrass during the previous year under more normal temperature and rainfall conditions. Photosensitization does not appear to have been observed in cattle on switchgrass but monitoring of younger animals grazing this Panicum species seems desirable.

The Susceptibility of Young Chickens, Ducks, and Turkeys to the Photosensitizing Effect of Ammi visnaga Seeds

Young chickens, ducks, and turkeys were exposed to sunlight and fed various amounts of Ammi visnaga seeds for 14 days in an attempt to induce photosensitization. In chickens, seeds at 1.25% in the diet had no effect whereas 3% induced mild signs of photosensitization within 6 to 8 days. No visible effects resulted in ducklings from 1.5, 3 and 6% in the diet, or in turkey poults from 3%. These differences appear to be due to differences between these avian species in the metabolism of the photodynamic agent.

Studies on erythropoietic protoporphyria

Erythropoietic protoporphyria, first reported in 1961, is an inherited metabolic disorder, characterized by cutaneous photosensitivity, normal urinary porphyrin levels and increased protoporphyrin IX concentrations in erythrocytes, plasma and faeces. Diagnosisin photosensitive patients is made by observing fluorescent erythrocytes under ultraviolet light microscopy or by quantitating erythrocyte protoporphyrin. This paper reportedresults of studies on six patients with this disorder, andon members of two affected families. These family studies provided evidence to support a dominant modeof inheritance, with a variable expressivity of thetrait causing a number of individuals to show no clinical signs of photosensitivity and only mild biochemical abnormalities, namely, small increases in erythrocyte or faecal prophyrin levels. Some of the many unanswered questions regarding erythropoietic protoporphyria were discussed, including the nature of the metabolic defect. It is likely that the accumulation of protoporphyrin is due to overproduction rather than to a block in the pathway of haem synthesis. Proposed studies in this field were outlined. The mechanism by which overproduction could arise from a constitutive operator mutation via increased enzyme synthesis was explained. The possible mechanism of production of the photosensitive skin reaction in erythropoietic protoporphyria was also discussed.

A THERAPEUTIC APPROACH TO ANERGIC, CHRONIC SCHIZOPHRENICS WITH TRIFLUOPERAZINE

Summary A relatively new, phenothiazine derivative, trifluoperazine was selected and its pharmacological study was carried out in terms of clinical efficacy and the usefulness of the drug, as a therapeutic approach to the so-called backward, anergic, withdrawn schizophrenic patients who have been refractory to the previous treatment. The drug was administered to 55 chronic schizophrenics who have been ill over 3 years (average: 8.2 years) and the duration of treatment ranged from 3 months to 12 months. A double-blind method was applied in this study and the patients were divided into 3 groups: A, the drug group during 3-month project, 30 cases, B, out-patient clinic basis, 15 cases, and C, the placebo group during 3-month project but after the project, received trifluoperazine, 10 cases. In rating the patients, “Psychiatric Evaluating Scale” (P.E.S.) and “Behavioral Rating Scale” (B.R.S.) were used for uniformity in assessing the therapeutic responses. Regarding the dosage of trifluoperazine, the effective daily dose ranged from 7.5 mg to 30 mg, maintenance dose ranged from 7.5 mg to 15 mg per day and the tolerable maximum dose administered in this study was 60 mg daily. No better result was obtained with the dose over 30 mg per day. The improvement rate of 3-month project in the drug group (Group A) was 56.6% and the result of 12-month follow up (60%) was about the same comparing with that of Group A. Generally, noticeable improvement occurred 2 or 3 weeks after the drug administration. In terms of target symptom effects, trifluoperazine proved to activate anergic, withdrawn chronic schizophrenics, particularly, in improving apathetic or dull affectivity, personal appearance, hostile and negativistic attitudes and delusions, hallucinations, psychomotor excitement, in some cases. In this study, no correlation between the occurrence of extra-pyramidal syndroms or other side effects and clinical improvement was found. Trifluoperazine caused various degrees of side effects, most frequently, tremor of extremities and akathisia at the dose over 7.5 mg or frequently at the dose of 20 mg per day. These side effects, however, in most cases, were manageable by the administration of anti-parkinsonian agent “Artane” or by lowering the dosage in some cases. On out clinic basis, prophylactic administration of “Artane” was needed in sensitive cases to a drug and the optimum dose ranged from 7.5 mg to 15 mg daily. Laboratory examinations were all within normal limits. There were no cases of clinical jaundice, agranulocytosis, convulsion and no cases with hypotensive crisis. None of the patients during the course of treatment showed the signs of photosensitivity.