Increased mitochondrial respiratory chain enzyme activities correlate with minor extent of liver damage in mice suffering from erythropoietic protoporphyria

Mitochondrial dysfunction might play a role in the pathogenesis of liver damage in erythropoietic protoporphyria (EPP). Changes in mitochondrial respiratory chain activities were evaluated in the Fech(m1pas)/Fech(m1pas) mouse model for EPP. Mice from different strains congenic for the same ferrochelatase germline mutation manifest variable degrees of hepatobiliary injury. Protoporphyric animals bred into the C57BL/6J background showed a higher degree of hepatomegaly and liver damage as well as higher protoporphyrin (PP) accumulation than those bred into the SJL/J and BALB/cJ backgrounds. Whereas mitochondrial respiratory chain activities remained unchanged in the liver of protoporphyric mice C57BL/6J, they were increased in protoporphyric mice from both SJL/J and BALB/cJ backgrounds, when compared to wild-type animals. Mitochondrial respiratory chain activities were increased in Hep G2 cell line after accumulation of PP following addition of aminolevulinic acid. As a direct effect of these elevated mitochondrial activities, in both hepatic cells from mutant mouse strains and Hep G2 cells, adenosine 5'-triphosphate (ATP) levels significantly increased as the intracellular PP concentration was reduced. These results indicate that PP modifies intracellular ATP requirements as well as hepatic mitochondrial respiratory chain enzymatic activities and further suggest that an increase of these activities may provide a certain degree of protection against liver damage in protoporphyric mice.     

Assessment of determinants of optimum performance of the CAST-2000 ELISA procedure

The Cellular Antigen Stimulation Test (CAST), a recent innovation in the laboratory detection of allergen sensitivity, is a functional assay based on the release of sulphidoleukotrienes (LTs) from allergen-activated circulating basophils. The current study was undertaken to establish optimum determinants of this procedure. The results demonstrate that treatment of blood with preservative-free heparin in polypropylene containers, and removal of erythrocytes by selective lysis with 0.83% ammonium chloride are excellent alternatives to the use of CAST venepuncture tubes and dextran, respectively. Similarly, decreasing and increasing the leucocyte concentration by 0.5- and 4-fold, respectively, as well as omission of interleukin-3 (IL-3) were also without significant effect. However, treatment of leucocyte suspensions with bacterial endotoxin (>1 microg/ml) activated the release of sulphidoleukotrienes from basophils and/or other types of leucocytes. The findings of this study are clearly relevant, both with respect to cost and performance, when implementing the CAST in clinical immunology laboratories.     

Intussusception in a preterm neonate; a very rare, major intestinal problem--systematic review of cases

Intussusception is an extremely rare disorder in preterm infants and it is often misdiagnosed as necrotizing enterocolitis. We report a case of intussusception in a 30-day-old preterm infant of 26 weeks of gestational age and a birthweight of 610 g who was diagnosed via abdominal ultra sonography. A systematic review of the literature was performed and reports on 23 previous cases were found. The presence of recognizable causes of intussusception in preterms, such as Meckel's diverticulum, bowel polypus, etc. was very infrequent. Comorbidity before and after intussusception is heterogeneous and related to prematurity. The intussusception is predominantly located in the small bowel (91.6%)--ileal or jejunal. The condition is misdiagnosed as NEC and managed conservatively until clinical deterioration occurs. A definitive diagnosis is thus established during abdominal surgery, which is usually delayed an average of 9.5 days from the onset of symptoms. Our case illustrates the capability of abdominal ultrasonography to establish early diagnosis of intussusception in the premature newborn.     

Depo medroxyprogesterone acetate (DMPA) and combined oral contraceptives and cervical carcinoma in-situ in women aged 50 years and under

Most low-resource settings depend on hormonal contraceptives for their family planning programmes and cervical cancer occurs in higher frequency in these populations. To determine whether hormonal contraception use increases cervical carcinoma in-situ (CIS) risk, a case-control study was conducted in the Kingston and St Andrew Corporate area of Jamaica, using 119 cases from the Jamaica Tumour Registry and 304 population controls matched on year of Papanicolaou (Pap) smear and clinic where Pap smear was obtained. While CIS cases were more likely to have 'ever used' combined oral contraceptives (COC) (OR = 1.4, 95% CI: 0.8, 2.5), depo-medroxyprogesterone acetate (DMPA) use was similar. Compared to women who never used hormonal contraceptives, the risk of CIS was elevated in: women who had used COCs five years or more (OR = 2.1, 95% CI: 1.0, 4.6), women who first used COC for less than 10 years prior to the interview (OR = 1.8, 95% CI: 0.9, 3.7) and women who were 18 to 24 years old when they first used COCs (OR = 1.8, 95% CI: 0.9, 3.4). Similarly, compared to women who never used DMPA, the risk of CIS was elevated in: women using DMPA five years or more (OR = 1.9, 95% CI: 0.7, 4.8), women reporting use within a year prior to interview (OR = 2.8, 95% CI: 0.7, 10.7) and women who initiated use of DMPA when they were 20 and 24 years old (OR = 1.4, 95% CI: 0.7, 3.1). These results suggest that if hormonal contraceptive use confers any risk of CIS, it is confined to long-term users. Increased risk in some groups, however, warrant further study.     

Amyloid myopathy presenting with distal atrophic weakness

Amyloid myopathy is a rare complication of primary amyloidosis usually presenting with proximal muscle weakness. We report a woman with multiple myeloma in whom marked atrophy and weakness of finger flexor muscles were the first manifestations of systemic amyloidosis. Muscle biopsy revealed amyloid angiopathy with deposits of lambda light chains in vessel walls. The recognition of amyloid myopathy is important because clinical symptoms may respond to chemotherapy.     

Possible benefits of calcitonin in the treatment of otosclerosis

This study shows the results obtained after treatment with intranasal calcitonin in 23 patients (36 ears) suffering from otosclerosis. 19.4% showed a hearing improvement upper of 10 dB. The gain was 32 dB in air conduction thresholds and 23 dB. In bone conduction. Tinnitus disappeared in 25% of cases suffering from tinnitus. Calcitonin tolerance was good, 8.7% of patients reported migraine. Authors recommended additional studies in order to evaluate the efficacy of this drug in the treatment of otosclerosis.     

Early-onset multisystem mitochondrial disorder caused by a nonsense mutation in the mitochondrial DNA cytochrome C oxidase II gene

We report the first nonsense mutation (G7896A) in the mtDNA gene for subunit II of cytochrome c oxidase (COX) in a patient with early-onset multisystem disease and COX deficiency in muscle. The mutation was heteroplasmic in muscle, blood, and fibroblasts from the patient and abundantly present in COX-deficient fibers, but less abundant in COX-positive fibers; it was not found in blood samples from the patient's asymptomatic maternal relatives. Immunoblot analysis showed a reduced concentration of both COX II and COX I polypeptides, suggesting impaired assembly of COX holoenzyme.