Acute effects of cocaine on ornithine decarboxylase activity in fetal and neonatal rat heart: evidence for cardiotoxicity

Fetal exposure to cocaine is associated with increased perinatal cardiac risk. In the current study, we examined the effects of acute cocaine administration on ornithine decarboxylase (ODC) activity in fetal and neonatal rat heart. ODC is a key regulatory enzyme in the control of cell differentiation and growth, and rapid changes in ODC are associated with the response to cell injury. Administration of 30 mg/kg s.c. of cocaine to pregnant rats on the 20th day of gestation caused acute elevation of fetal cardiac ODC that persisted throughout the ensuing 24 h. In contrast, the same dose given directly to neonatal rats the day after birth evoked only a short-term (1-h) stimulation of ODC that was reversed by 4 h after treatment. By 4 days of age and subsequently, cocaine was unable to elicit acute stimulation of heart ODC and only evoked inhibition of enzyme activity. Elevated progesterone levels during pregnancy have been shown to sensitize the maternal myocardium to cocaine-induced catecholaminergic effects; the greater sensitivity of fetal heart ODC to cocaine, as compared to neonatal heart, supports the hypothesis that similar enhancement of fetal cardiac irritability can contribute to cocaine-induced cell damage.     

Incidence of nasal carriers of Staphylococcus aureus in and outside hospital environment and antibiotic sensitivity of isolated staphylococcus strains

This study was carried out on 100 nasal swabs collected from medical personnel (nurses and doctors) and patients inside hospital environment and also from 50 individuals outside hospital. The swabs were inoculated on different culture media for isolation of /staphylococci which were further identified as S. aureus either by classic bacteriologic methods or by one of rapid screening test of S. aureus. The isolated strains were tested for antibiotic sensitivity to some of B-Lactam antibiotics and to other antibiotics. The results showed that significantly higher percentage of coagulase + ve Staph. were isolated from newborn nursery (90%), operating theatre (71.4%) and hemodialysis unit (60%) than those isolated from intensive care unit, cancer chemotherapy, surgery, chest, internal medicine departments (25%, 26.6%, 31.2%, 33.3%, 50%) respectively. It also showed significant difference in isolation rate between persons at the hospital (patients, doctors and nurses) 44% and controls (normal population) 26%. Most isolates of coagulase + ve Staph. were resistant to penicillin G (93.2%), Streptomycin (77.3%), tetracycline (61.4%) and sensitive to cefamandole (95.4%). All coagulase+ve Staph. isolates were resistant to sulphonamide and methicillin and all sensitive to vancomycin.     

Quality of life and pain in patients with recurrent breast and gynecologic cancer

The kinetic mechanisms of the binding to tubulin of colchicine and eight different analogues have been studied to elucidate details of the recognition mechanism. All of the analogues follow a two step binding mechanism i.e. binding occurs via an initial step with low affinity, followed by an isomerisation of the initial complex leading to the final high affinity state. For several analogues the kinetic and thermodynamic data of both processes are compared here. For all the analogues the delta G1 degree of initial binding at 25 degrees C varies between -13.3 and -28.8 kJ. mol-1. For the second step delta G2 degrees varies between -2.4 and -27 kJ. mol-1. These limited ranges of free energy change are, however, obtained by a great variety of enthalpy changes and compensatory entropy changes. Comparison of the data for the first and second steps indicates that structural alterations of the drugs always change the thermodynamic parameters of the two steps, and the changes in the first and the second steps are in opposite directions. The fact that this range of experimental behaviour can be incorporated into a general mechanism encourages the extension of these investigations to other colchicine analogues and related compounds with potential pharmaceutical applications.     

Biochemistry of coenzyme B12-dependent glycerol and diol dehydratases and organization of the encoding genes

Glycerol and diol dehydratases exhibit a subunit composition of alpha 2 beta 2 gamma 2 and contain coenzyme B12 in the base-on form. The dehydratase reaction proceeds via a radical mechanism. The dehydratases are subject to reaction inactivation by the substrate glycerol which is caused by a cessation of the catalytic cycle because coenzyme B12 is not regenerated, instead 5'-deoxyadenosine and a catalytically inactive cobalamin are formed. The genetic organization of the dehydratase genes is quite similar in all organisms. Downstream of the dehydratase genes an open reading frame encoding a polypeptide of approximately 600 amino acids was identified which is apparently involved in the reactivation of suicide-inactivated enzyme.     

Feasibility study of repeated fluorescent in-situ hybridization in the same human blastomeres for preimplantation genetic diagnosis

In order to increase the number of chromosomes examined in each blastomere, we have developed a repeated fluorescent in-situ hybridization (FISH) procedure by which six or more chromosomes can be analysed per blastomere of a human embryo. Three consecutive FISH procedures with directly-labelled fluorescent Vysis DNA probes were carried out for examination of chromosomes X, Y, 11, 13, 18 and 21 in the same blastomeres (n = 126) and lymphocytes (n = 164). Based on the initial number of nuclei, the percentages of nuclear loss and presence of signals were 3 and 92% respectively in blastomeres; 6 and 91% respectively in lymphocytes after the first FISH; 7 and 87% respectively in blastomeres and 10 and 86% respectively in lymphocytes, after the second FISH. These percentages were 13 and 78% respectively in blastomeres and 14 and 81% respectively in lymphocytes after the third FISH. The FISH procedure was repeated successfully in a couple for preimplantation genetic diagnosis of chromosomal aneuploidies in biopsied blastomeres of their embryos in our clinic. In conclusion, it is feasible to carry out repeated FISH procedures in the same blastomeres. Six or more chromosomes of a single blastomere may be examined using this procedure.     

Laparoscopically assisted extracorporeal neosalpingostomy. A case report

Primary intestinal lymphangiectasia is characterized by dilated small bowel lymphatics and loss of lymph into the bowel lumen resulting in hypoproteinaemia and oedema. Some patients have a more generalized lymphatic abnormality associated with lymphoedema of the limbs and chylous pleural effusions. There is no specific treatment although enteric protein loss may decrease with a low-fat diet. This report describes a patient with severe primary intestinal lymphangiectasia, associated with limb oedema and recurrent pleural effusions, who responded to treatment with octreotide. Before starting octreotide she required weekly intravenous albumin infusions to maintain the serum albumin above 20 g/l. Bilateral pleural effusions repeatedly reaccumulated despite pleurectomy and subsequently tetracycline pleurodesis. Treatment with octreotide, 200 microg twice daily, resulted in a reduction in enteric protein loss from 16 to 4.1% in 5 days (normal less than 1%) and the serum albumin was maintained between 22 and 26 g/l without the need for albumin infusion. Oedema in the arms resolved completely and the pleural effusions did not reaccumulate. The mechanism of action of octreotide in this condition appears to be due to a reduction in gut protein loss and another, as yet unidentified, action.     

Characterization of distinct human endometrial carcinoma cell lines deficient in mismatch repair that originated from a single tumor

The role of specific mismatch repair (MMR) gene products was examined by observing several phenotypic end points in two MMR-deficient human endometrial carcinoma cell lines that were originally isolated from the same tumor. The first cell line, HEC-1-A, contains a nonsense mutation in the hPMS2 gene, which results in premature termination and a truncated hPMS2 protein. In addition, HEC-1-A cells carry a splice mutation in the hMSH6 gene and lack wild-type hMSH6 protein. The second cell line, HEC-1-B, possesses the same defective hMSH6 locus. However, HEC-1-B cells are heterozygous at the hPMS2 locus; that is, along with carrying the same nonsense mutation in hPMS2 as in HEC-1-A, HEC-1-B cells also contain a wild-type hPMS2 gene. Initial recognition of mismatches in DNA requires either the hMSH2/hMSH6 or hMSH2/hMSH3 heterodimer, with hPMS2 functioning downstream of damage recognition. Therefore, cells defective in hPMS2 should completely lack MMR (HEC-1-A), whereas cells mutant in hMSH6 only (HEC-1-B) can potentially repair damage via the hMSH2/hMSH3 heterodimer. The data presented here in HEC-1-B cells illustrate (i) the reduction of instability at microsatellite sequences, (ii) a significant decrease in frameshift mutation rate at HPRT, and (iii) the in vitro repair of looped substrates, relative to HEC-1-A cells, illustrating the repair of frameshift intermediates by hMSH2/hMSH3 heterodimer. Furthermore, the role of hMSH2/hMSH3 heterodimer in the repair of base:base mismatches is supported by observing the reduction in base substitution mutation rate at HPRT in HEC-1-B cells (hMSH6-defective but possessing wild-type hPMS2), as compared with HEC-1-A (hMSH6/hPMS2-defective) cells. These data support a critical role for hPMS2 in human MMR, while further defining the role of the hMSH2/hMSH3 heterodimer in maintaining genomic stability in the absence of a wild-type hMSH2/hMSH6 heterodimer.     

Evidence for the presence of both P1 and P2 purinoceptors in the rat myometrium

1. Adenosine, adenosine triphosphate (ATP) and some stable analogues of adenosine inhibited field stimulation-induced contractions of the uterus from rats treated with oestradiol cypionate (20 micrograms/kg, s.c.) 1 day previously. Adenosine was twice as potent as ATP; both were potentiated by dipyridamole (10 mumol/L). 2. The order of agonist potency of adenosine and its analogues was: 5'-N-ethylcarboxamidoadenosine (NECA) > N6-cyclohexyladenosine > or = R-phenylisopropyladenosine = S-phenylisopropyladenosine = 2-chloroadenosine > or = adenosine > or = ATP > > 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine. This order suggests the presence of P1 purinoceptors of the A2B subtype. 3. Responses to agonists were antagonized to differing extents by the P1 purinoceptor antagonist 8-phenyltheophylline (10 mumol/L). 4. In uterine preparations from rats pretreated for 2 days with oestrogen (20 micrograms/kg, s.c.) and for 1 day with progesterone (3 mg/animal, s.c.), the inhibitory potencies of adenosine and NECA were reduced, indicating hormonal regulation of uterine responsiveness to P1 purinoceptor agonists. 5. Stable analogues of ATP caused contractions of unstimulated myometrial preparations from oestrogen-treated animals, indicating activation of a P2 purinoceptor, possibly of the P2X subtype, because of the relative order of potency was alpha, beta-methylene ATP > beta, gamma-methylene ATP = ATP = 2-methylthio ATP.     

Thermafil obturation: a literature review

A review of the literature pertaining to the use of Thermafil Endodontic Obturators is presented in this article. Addressed are such concerns as apical microleakage, biocompatibility, coronal leakage, post space considerations, retreatment issues, surgical factors, and clinical evaluations of Thermafil; included are the authors' conclusions concerning its clinical use.