α2-adrenoceptor blockade,pituitary-adrenal hormones,and agonistic interactions in rats

The effects of adrenergic activation on aggressiveness and the aggression induced endocrine changes were tested in rats. α₂ adrenoceptor blockers were used for enhancing activation of the adrenergic system, and changes in aggressiveness were tested in resident-intruder contests. Three experiments were conducted. In experiment 1, saline injected rats responded to the presence of an opponent by aggression and the increase in plasma ACTH and corticosterone. Intraperitoneal administration of 1 mg/kg CH-38083 (an α₂ adrenoceptor antagonist) produced a several fold increase in clinch fighting and mutual upright scores, and also further enhanced the plasma ACTH and corticosterone response. In experiment 2, the effect of three doses (0.5, 1 and 2 mg/kg) of three different α₂ adrenoceptor blockers CH-38083, idazoxan and yohimbine were tested. All the substances increased aggression at 0.5 and 1 mg/kg; at 2 mg/kg the effect of idazoxan and yohimbine disappeared, while with CH-38083 an additional increase was obtained. In yohimbine treated animals the enhancement of aggression was reduced already at 1 mg/kg. In experiment 3, indomethacin, a potent inhibitor of the catecholamine-induced ACTH release completely abolished the effects of the α₂ adrenoceptor antagonist CH-38083: the intensity of agonistic interactions, as well as ACTH and corticosterone plasma concentrations, returned to control levels. The possible role of catecholamines and the stress hormones in the activation of aggression is discussed.     

Characterization of a highly polymorphic marker adjacent to the SLC4A1 gene and of kidney immunostaining in a family with distal renal tubular acidosis.

BACKGROUND: Mutations in the human SLC4A1 (AE1/band 3) gene are associated with hereditary spherocytic anaemia and with distal renal tubular acidosis (dRTA). The molecular diagnosis of AE1 mutations has been complicated by the absence of highly polymorphic genetic markers, and the pathogenic mechanisms of some dRTA-associated AE1 mutations remain unclear. Here, we characterized a polymorphic dinucleotide repeat close to the human AE1 gene and performed an immunocytochemical study of kidney tissue from a patient with inherited dRTA with a defined AE1 mutation. METHODS: One CA repeat region was identified in a phage P1-derived artificial chromosome (PAC) clone containing most of the human AE1 gene and the upstream flanking region. We determined its heterozygosity value in multiple populations by PCR analysis. Genotyping of one family with dominant dRTA identified the AE1 R589H mutation, and family member genotypes were compared with the CA repeat length. AE1 and vH(+)-ATPase polypeptides in kidney tissue from an AE1 R589H patient were examined by immunocytochemistry for the first time. RESULTS: This CA repeat, previously reported as D17S1183, is approximately 90 kb upstream of the AE1 gene and displayed considerable length polymorphism, with small racial differences, and a heterozygosity value of 0.56. The allele-specific length of this repeat confirmed co-segregation of the AE1 R589H mutation with the disease phenotype in a family with dominant dRTA. Immunostaining of the kidney cortex from one affected member with superimposed chronic pyelonephritis revealed vH(+)-ATPase-positive intercalated cells in which AE1 was undetectable, and proximal tubular epithelial cells with apparently enhanced apical vH(+)-ATPase staining. CONCLUSIONS: The highly polymorphic dinucleotide repeat adjacent to the human AE1 gene may be useful for future studies of disease association and haplotype analysis. Intercalated cells persist in the end-stage kidney of a patient with familial autosomal dominant dRTA associated with the AE1 R589H mutation. The absence of detectable AE1 polypeptide in those intercalated cells supports the genetic prediction that the AE1 R589H mutation indeed causes dominant dRTA.     

Narrowband UVB therapy for vitiligo: does the repigmentation last?

BACKGROUND: Since 1997, a number of trials have shown promising results in treating generalized vitiligo with narrowband ultraviolet B (UVB) both in adults and children. However, there is little knowledge concerning the duration and permanency of the treatment-induced repigmentation. OBJECTIVE: Our main objective was to perform a follow-up trial of successfully treated patients receiving narrowband UVB for generalized vitiligo. METHODS: We have investigated to what degree the treatment-induced repigmentation remains stable for up to 2 years post-treatment. We performed an initial open trial including 31 patients with generalized vitiligo. They received narrowband UVB thrice weekly for up to 12 months. Patients experiencing > 75% repigmentation were defined responders and were included in the follow-up trial. Responders were followed every 6 months for up to 2 years after cessation of treatment. We observed the pigmentation status and registered any changes indicating loss of pigmentation and relapse. RESULTS: Eleven of the 31 treated patients were included in the follow-up trial. Six patients had relapse and five patients had stable response 24 months after cessation of treatment. Four out of six relapses were within 6 months post-treatment. CONCLUSION: In our study population of 31 patients with generalized vitiligo, five patients (16%) experienced > 75% stable repigmentation 2 years after cessation of a treatment programme of up to 1 years narrowband UVB therapy.     

Ongoing pregnancies after intracytoplasmic injection using cryopreserved testicular spermatozoa

We report two clinical pregnancies occurring after intracytoplasmic sperm injection (ICSI) using cryopreserved spermatozoa obtained from testicular biopsy, made in two different infertility situations in our clinic. The first patient showed a secretory azoospermia associated with elevated serum follicular stimulating hormone (FSH) level and spermiogenesis maturation arrest. The second patient was affected by azoospermia resulting from bilateral epididymal obstruction. Spermatozoa present in the wet preparation of testicular biopsy made on the day of scrotal exploration were cryopreserved within the testicular tissue for both men. Intracytoplasmic injections were performed at a later date, using spermatozoa prepared from frozen-thawed tissues. In each case, three embryos were obtained and transferred in utero. The transfers resulted in a twin pregnancy for the first case, and in a singleton pregnancy for the second. Living foetuses were seen in the ultrasound scan at the 7th week and both pregnancies are proceeding to date beyond 30 weeks without complications.