Effect of irradiation at the early foetal stage on adult brain function of mouse: learning and memory

PURPOSE: To study the long-term effect of early foetal irradiation on the learning and memory in the adult mouse. MATERIALS AND METHODS: The abdominal area of pregnant Swiss albino mice was exposed to a single dose of 0.25-1.5Gy gamma-radiation on the 14th day of gestation and the mice were left to deliver their offspring. At 6 months of age, the learning and memory functions of the F(1) mice were tested by hole-board activity, conditioned avoidance response and radial arm maze performance. The animals were again subjected to the radial arm maze test at 12 and 18 months of age. RESULTS: There was a significant dose-dependent decrease in the learning ability and memory retention of 6-month-old mice at doses > 0.25Gy. The significant changes persisted to 18 months of age in mice exposed to >or= 0.5Gy. All changes showed a linear dose-response at doses < 1Gy. CONCLUSIONS: The gestational day 14 of Swiss albino mice is a sensitive stage in brain development to gamma-ray-induced impairment of learning and memory during the adult life. Permanent deficits in these functions can be induced by a dose of approximately 0.5Gy at this stage, when the developmental activity of the cerebral cortex is at its peak.     

Sexual life style, drug habit and socio-demographic status of drug addicts in Bangladesh

The sexual life style, drug habit and socio-demographic status of 253 male hospitalized drug addicts were investigated. This study was conducted during the period June 1997 to July 1998, and each case was selected by the random sampling method. The research instrument was an interviewer-administered questionnaire, the sexual habits, number and quality of sex partners, use of condoms, sexually transmitted diseases, etc., were considered as indicators of the sexual life style of the drug addicts. Eighty-eight percent (n=233) of the addicts were heterosexual. Bisexuality was found only in 7% (n=18) of the addicts. Eighty-seven percent (n=240) of the addicts have multiple sex partners of either commercial or residential category. Most of the drug addicts (72%,n=181) did not use condoms. Fifty-seven percent (n=145) of the addicts were observed to have sexual diseases. As indicators of a drug habit, starting drug, choice of drug, period of addiction, sharing of needles, etc., were included. Cannabis was the starting substance for 59% (n=149) of the addicts. Heroin was the drug of choice for 60% (n=157) addicts. A single drug was taken only by 8% (n=20) of the addicts and the remaining 92% (n=233) took multiple drugs. The drug addicts (n=97) who used mostly injection (87%,n=84) shared needles. Education, occupation, income, age, marital status, influencing factors for addiction were considered as socio-demographic characteristics. Young adults (79%,n=199), secondary educated (46%,n=116), low-mid income (60%,n=150), businessmen (46%,n=150) and married (60%,n=151) people were found highly involved in addiction. Self-curiosity and a friend's incitement were revealed as the most important influencing factors for taking drugs.     

Mutagenesis induced by a single 1,N6-ethenodeoxyadenosine adduct in human cells

To study the genotoxic properties of 1,N6-ethenodeoxyadenosine (epsilondA) in human cells, a novel site-specific mutagenesis approach was developed, in which a single DNA adduct was uniquely placed in either strand of a shuttle plasmid vector. The analysis of progeny plasmid derived from the modified strand shows that epsilondA, when incorporated into the position of the second A of 5'-CAA (codon 61 of the ras gene), is mutagenic in human cells, inducing A-->T, A-->G, and A-->C mutations. The efficient induction of A-->T transversions in experiments using modified double- and singlestranded DNA substrates supports the hypothesis that A:T-->T:A transversions in human and animal tumors induced by vinyl compounds reflect misinsertion of dAMP opposite this adduct. Mutagenic events were similar when the adduct was incorporated into either the leading or the lagging strand. EpsilondA was more mutagenic than 8-oxodeoxyguanosine, which induced targeted G-->T transversions in HeLa cells. In Escherichia coli, epsilondA did not significantly miscode (<0.27%) even in the presence of induced SOS functions.     

Floctafenine (Idarac) in the management of rheumatoid arthritis.

A double-blind controlled cross-over trial comparing floctafenine 1.6 g daily with soluble aspirin 4.0 g daily and matching placebo, in 48 patients suffering from rheumatoid arthritis, is reported. Floctafenine and aspirin gave statistically significant reduction in morning stiffness, grip strength and better subjective assessment than the placebo. There was no difference in the relief of pain between the three treatments under the conditions of this trial where paracetamol was allowed as an additional escape analgesic. During the period of aspirin therapy there was a higher indicence of concurrent complaints, faecal occult blood loss and a reduction in haemoglobin. An open long-term study in 12 rheumatoid patients receiving floctafenine 1.6 g daily for 3--6 months showed satisfactory management of their clinical condition. There were no significant or serious side-effects or change in biochemical or haematological parameters, and patients completed their course of therapy.     

Correlation of serum parathormone level with biochemical parameters in chronic renal failure

A prospective study was carried out to assay the level of serum intact parathormone and its correlation with biochemical parameters in patients with chronic renal failure (CRF). The study included 64 children (44 with CRF, and 20 age and sex matched controls). Serum intact parathormone (iPTH), serum creatinine, urea, calcium, inorganic phosphate and alkaline phosphatase were estimated. Creatinine clearance (Ccr) was estimated by Schwartz formula. Patients with CRF were divided into four groups based on their Ccr (mild CRF with mean Ccr 59.17 +/- 1:18.53 mL/min/1.73 m2 (n = 6) moderate CRF with mean Ccr 34.98 +/- 7.75 mL/min/1.73 m2 (n = 7); severe CRF with mean Ccr 17.71 +/- 5.40 mL/min/1.73 m2 (n = 15); and end-stage renal disease with mean Ccr 6.46 +/- 1.71 mL/min/1.73 m2 (n = 16). Mean serum iPTH levels were 93.00 +/- 46.62 pg/mL in CRF and 16.52 +/- 9.35 pg/mL in controls. Groupwise mean serum (iPTH) levels were 48.50 +/- 4.76, 67.29 +/- 7.91, 82.42 +/- 9.67 and 130.66 +/- 58.74 pg/mL in mild, moderate, severe CRF and endstage renal failure respectively. Mean serum iPTH level of CRF (93.00 +/- 46.42 pg/mL) negatively correlated with mean Ccr (22.02 +/- 18.53 mL/min/l.73 m2) (P < 0.001) and mean serum calcium (7.30 +/- 1.02 mg/dL) (P < 0.001) and positively correlated with mean inorganic phosphate (5.76 +/- 1.1 mg/dL) (P < 0.05) and mean alkaline phosphatase (355.14 +/- 185.53 UL) (P < 0.001). We conclude that increased iPTH level occur even early in the course of CRF and progressive hypocalcemia and hyperphosphatemia are the initiating factors for the development of hyperparathyroidism.     

Serum hyaluronate as a non-invasive marker of hepatic fibrosis and inflammation in HBeAg-negative chronic hepatitis B

Background  

HBV infection is a serious global heath problem. It is crucial to monitor this disease more closely with a non-invasive marker in clinical trials. We aimed to evaluate the predictive value of serum hyaluronate for the presence of extensive liver fibrosis and inflammation.     

Molecular mediators of hypoxic-ischemic injury and implications for epilepsy in the developing brain

Perinatal hypoxia-ischemia (HI) is the most common cause of cerebral palsy, and an important consequence of perinatal HI is epilepsy. Epilepsy is a disorder in which the balance between cerebral excitability and inhibition is tipped toward uncontrolled excitability. Selected neuronal circuits as well as certain populations of glial cells die from the excitotoxicity triggered by HI. Excitotoxicity, a term referring to cell death caused by overstimulation of the excitatory glutamate neurotransmitter receptors, plays a critical role in brain injury caused by perinatal HI. Ample evidence suggests distinct differences between the immature and mature brain with respect to the pathology and consequences of hypoxic-ischemic brain injury. Thus, the intrinsic vulnerability of specific cell types and systems in the developing brain is particularly important in determining the final pattern of damage and functional disability caused by perinatal HI. These patterns of neuronal vulnerability are associated with clinical syndromes of neurologic disorders such as cerebral palsy, epilepsy, and seizures. Recent studies have uncovered important molecular and cellular aspects of hypoxic-ischemic brain injury. The cascade of biochemical and histopathological events initiated by HI can extend for days to weeks after the insult is triggered, which may provide a "therapeutic window" for intervening in the pathogenesis in the developing brain. Activation of apoptotic programs accounts for the majority of HI-induced pathophysiology in neonatal brain disorders. New experimental approaches to protecting brain tissue from the effects of neonatal HI include administration of neuronal growth factors and effective inhibition of the death effector pathways, such as caspase cascade, and their downstream targets, which execute apoptosis and/or induction of their regulatory cellular proteins. Our recent findings that a novel neuronal protein, neuronal pentraxin 1 (NP1), is induced following HI in neonatal brain and that NP1 gene silencing is neuroprotective suggest that NP1 could be a new molecular target in the central neurons for preventing HI injury in developing brain. Most importantly, the specific interactions between NP1 and the excitatory glutamate receptors and their colocalization further implicate a role for this novel neuronal protein in the excitotoxic cascade. Recent experimental work suggests that these approaches may be effective during a longer therapeutic window after the insult, as they are acting on events that are relatively delayed, creating the potential for therapeutic interventions for these lifelong neurological disabilities.     

Usefulness of 16S rDNA polymerase-chain-reaction (PCR) in the intraoperative detection of infection in revision of failed arthroplasties

AIM: In this study the accuracy of the 16S DNA polymerase chain reaction (PCR) in revision arthroplasties was compared to that of conventional bacterial culture when correlated to intraoperative histological findings. Furthermore, the influence of antibiotic treatment and different ways of collecting samples was evaluated. METHOD: In a prospective study we collected samples of tissues, aspiration fluids and swabs during revision arthroplasty surgery and examined them with PCR as well as conventional bacterial culturing methods. Also, we correlated these two methods with the histological findings of intraoperative tissue samples. Two independent examiners evaluated the samples according to the criteria of Mirra et al. Sensitivity, specificity, positive and negative prediction value and the accuracy were calculated for the molecular biological and culture methods. Three groups were defined to evaluate the influence of accompanying antibiotic treatment and the way of collecting the microbiological samples. RESULTS: Nine periprosthetic infections could be detected by PCR as well as by conventional bacterial culturing. Correlated with the 25 positive histological findings this resulted in a sensitivity of 0.36, a specificity of 1.0, a negative prediction value of 0.61, a positive prediction value of 1.0 and an accuracy of 0.68 for both methods. Swabs compared to aspiration fluids and tissues samples showed the highest sensitivity with both methods. No higher sensitivity of PCR compared to conventional bacterial culturing could be observed in patients with accompanying antibiotic treatment. CONCLUSION: Although PCR is more rapidly available for the diagnosis of periprosthetic infection, a definite advantage of this more expensive method could not be demonstrated in view of the same low sensitivity of PCR and conventional bacterial culturing.     

D-Allose has a strong suppressive effect against ischemia/reperfusion injury: a comparative study with allopurinol and superoxide dismutase

Background/Purpose d-Allose, a rare sugar, is one of the potent inhibitors of ischemia/reperfusion injury of the rat liver. To investigate the potency of this powerful agent we examined its effect against ischemia/reperfusion injury and compared it to that of allopurinol and superoxide dismutase.Methods Male Lewis rats were given water ad libitum preoperatively for 12h and anesthetized by isoflurane inhalation anesthesia. Drugs were administered through a polyethylene catheter inserted into the portal vein for 2h (d-allose), 10min (allopurinol), or 5min (superoxide dismutase) before ischemia, and the livers were then subjected to 70% ischemia, induced by crossclamping the vessels to the lateral and median lobes of the liver for 90min. Rats were divided into four groups: group 1, pretreated with vehicle (normal saline); group 2, treated with d-allose; group 3, treated with allopurinol; and group 4, treated with superoxide dismutase. The effects of the drugs were evaluated by liver hemodynamics, neutrophil count, myeloperoxidase, liver enzymes, and histological studies.Results d-Allose improved liver hemodynamics (P < 0.001) and postischemic animal survival (P < 0.05) significantly compared with the control group and nonsignificantly compared with the allopurinol and superoxide dismutase groups. Myeloperoxidase activity in the postischemic liver tissue was decreased significantly (P < 0.05) by d-allose compared with all other treatment and control groups. Neutrophil count was also significantly (P < 0.05) decreased in the d-allose group compared with than that in the control group, as well as the superoxide dismutase group. Only d-allose produced a statistically significant decrease in the level of liver enzymes, compared with levels in the control group.Conclusions The moderately protective effect of d-allose, which caused no clinical side effects, is encouraging. d-Allose had the best protective effect against neutrophil-related postischemic injury of the liver tissue, followed by allopurinol and superoxide dismutase. However, a more extensive study is needed to ensure the effects as well as the mechanisms of the effect of this rare sugar.