Graph theory for automatic structural recognition in molecular dynamics simulations.

Graph theory algorithms have been proposed in order to identify, follow in time, and statistically analyze the changes in conformations that occur along molecular dynamics (MD) simulations. The atomistic granularity level of the MD simulations is maintained within the graph theoric algorithms proposed here, isomorphism is a key component together with keeping the chemical nature of the atoms. Isomorphism is used to recognize conformations and construct the graphs of transitions, and the reduction in complexity of the isomorphism has been achieved by the introduction of "orbits" and "reference snapshots." The proposed algorithms are applied to MD trajectories of gas phase molecules and clusters as well as condensed matter. The changes in conformations followed over time are hydrogen bond(s), proton transfer(s), coordination number(s), covalent bond(s), multiple fragmentation(s), and H-bonded membered rings. The algorithms provide an automatic analysis of multiple trajectories in parallel, and can be applied to ab initio and classical MD trajectories alike, and to more coarse grain representations.

Outcome of pregnancy in type 1 diabetic patients treated with insulin lispro or regular insulin: an Italian experience.

Some studies have shown that fetal outcome observed in patients using insulin lispro is much the same as in pregnant women using regular insulin. This study aims to analyze the Italian data emerging from a multinational, multicenter, retrospective study on mothers with type 1 diabetes mellitus before pregnancy, comparing those treated with insulin lispro for at least 3 months before and 3 months after conception with those treated with regular insulin. The data collected on pregnant women with diabetes attending 15 Italian centers from 1998 to 2001 included: HbA1c at conception and during the first and third trimesters, frequency of severe hypoglycemic episodes, spontaneous abortions, mode and time of delivery, fetal malformations and mortality. Seventy-two diabetic pregnancies treated with lispro and 298 treated with regular insulin were analyzed, revealing a trend towards fewer hypoglycemic episodes in the former, who also had a significantly greater reduction in HbA1c during the first trimester. The rate of congenital malformations was similar in the offspring of the two groups of women treated with insulin lispro or regular insulin. These findings suggest that insulin lispro could be useful for the treatment of hyperglycemia in type 1 diabetic pregnant women.

An interdisciplinary approach to investigate the impact of cobalt in a human keratinocyte cell line.

Since in nuclear power plants, risks of skin contact contamination by radiocobalt are significant, we focused on the impact of cobalt on a human cutaneous cell line, i.e. HaCaT keratinocytes. The present paper reports an interdisciplinary approach aimed at clarifying the biochemical mechanisms of metabolism and toxicity of cobalt in HaCaT cells. Firstly, a brief overview of the used instrumental techniques is reported. The following parts present description and discussion of results concerning: (i) toxicological studies concerning cobalt impact towards HaCaT cells (ii) structural and speciation fundamental studies of cobalt-bioligand systems, through X-ray absorption spectroscopy (XAS), ab initio and thermodynamic modelling (iii) preliminary results regarding intracellular cobalt speciation in HaCaT cells using size exclusion chromatography/inductively coupled plasma-atomic emission spectroscopy (SEC/ICP-AES) and direct in situ analysis by ion beam micropobe analytical techniques.

Effects of tizanidine administration on precipitated opioid withdrawal signs in rats.

An opioid withdrawal syndrome was precipitated by naloxone administration in rats treated with morphine. The withdrawal caused alteration of several physiological signs. The aim of the study was to investigate whether the altered physiological profiles were modified by utilising tizanidine, an alpha 2 adrenergic receptor agonist which is capable of affecting faecal and urinary excretion, rectal temperature, pain threshold levels and salivation. To induce an opioid withdrawal syndrome, morphine was administered in three daily intraperitoneal injections for four days at doses of 9, 16 and 25 mg/kg (1st day), 25, 25 and 50 mg/kg (2nd day), 50, 50 and 50 mg/kg (3rd day) and 50, 50 and 100 mg/kg (4th day): naloxone was injected (30 mg/kg) i.p. 180 min after the last morphine injection. Tizanidine was administered orally at 0.17, 0.35 and 0.7 mg/kg, 60 min after the last morphine injection. Signs such as faecal and urine excretion, rectal temperature and latency times to thermal stimulus, salivation, jumping and wet dog shakes were affected in different ways by morphine, naloxone, tizanidine and by the combination of these agents. Notably, the administration of tizanidine in rats receiving morphine and naloxone decreased the intensity of certain withdrawal symptoms, including altered excretion of faeces and urine, salivation and wet dog shake behavior. Body temperature levels and nociceptive threshold values were also modified. The effects caused by tizanidine administration may be due to its alpha 2 receptor agonist activity interfering with a mechanism involved in the regulation of these previously mentioned withdrawal symptoms. Thus, the use of this drug may be indicated as a possible control of the acute phase of opioid withdrawal in heroin addicts.

Modulation of neutrophil functions by a beta-interferon of human origin.

The effects of a beta interferon (beta-IFN) of human origin on different parameters of human neutrophil functioning were evaluated in vitro. In the concentration range 10(2)-10(4) IU/ml beta-IFN enhanced superoxide anion (O2-) production evoked by the peptide N-formylmethionyl-leucylphenylalanine (FMLP), 10(-7) M, when O2- production elicited by FMLP in the absence of beta-IFN treatment was 2.43 +/- 0.32 nmol cytochrome C reduced/10(6) cells/min. The enhancement afforded by 10(3) and 10(4) IU/ml beta-IFN was statistically significant. When FMLP-induced O2- generation was 4.55 +/- 0.3 nmol cytochrome C reduced/10(6) cells/min, no increase was detected after beta-IFN treatment. Phagocytosis was enhanced by beta-IFN in one case, with no effect in four others. Chemotaxis was not affected by exposure to beta-IFN. These results indicated that beta-IFN could exert modulating effects on some neutrophil functions that varied according to the extent of cell response to the stimuli.

Bacillus subtilis spores as a natural pro-host oral agent. Preliminary data in children.

The commercial preparation of Bacillus subtilis spores may be considered within the classification of biological response modifiers (BRM's) and included among exogenous natural substances. Recently we decided to study the effect of a long-term B. subtilis spores oral treatment in children suffering from recurrent infectious diseases of the respiratory tract. Fifty-three children 5-9 years old have been studied. The clinical valuative parameter was the number of days of absence from school during a 4-month period. In another group of 12 diseased children, mean age 5.5 yrs we recently initiated a laboratory immunological evaluation of peripheral lymphomonocytes in relation to an oral treatment with B. subtilis spores for at least 2 months. Our results show that B. subtilis spore therapy significantly reduced the frequency of respiratory tract infections in the group of treated children. In addition, preliminary immunological laboratory evaluation demonstrated a complete return to the normal lymphomonocyte status after at least 2 months of treatment with B. subtilis spores.

Arterial hypertension and microalbuminuria in IDDM: the Italian Microalbuminuria Study.

Arterial hypertension and poor glycaemic control are central to the development of microalbuminuria in insulin-dependent diabetes mellitus (IDDM). Recent consensus has established sensitive criteria for their detection and treatment, although the proportion of patients who may benefit is unclear. Between 1988 and 1990, we measured urinary albumin to creatinine concentration ratio (A/C) in 3,636 adult out-patients with IDDM of more than 3 years duration, serum creatinine under 133 mumol/l and who were not undergoing antihypertensive treatment. A/C indicating microalbuminuria (> or = 2.38/2.96 mg/mmol, male/female) was found in 620 of 3,451 patients without proteinuria, and associated with hypertension (blood pressure > or = 140 and/or 90 mmHg; p = 0.0016; rate: 39.6%), independent of diabetes duration (p = 0.0082) and male gender (p = 0.0350; relative risk = 1.16; 95% confidence interval: 1.01-1.32). Hypertension was less common among those with normal A/C (27.5%, p < 0.0001) but was positively related with diabetes duration. Of the 1,015 patients with A/C > or = 2.0 mg/mmol 529 were reexamined. Glycated haemoglobin levels exceeded 3 SD above the mean of normal in 84.3% of the 198 microalbuminuric patients (AER = 20-200 micrograms/min), but were comparably poor (79.2%) in normoalbuminuria. Duration of diabetes was inversely related to glycated haemoglobin only in microalbuminuria (0.05 < p < 0.1). Intervention to lower blood pressure remains mainly restricted to those patients with long-term diabetes and slower development of kidney disease. Near-normalisation of glycaemia remains the priority for the majority of patients with microalbuminuria.