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Biomedical subjects

M Mainardi

Publications and source records attributed to M Mainardi.

At least 19 recordsLinked to original sources

Polymorphisms in the CCR5 promoter region influence disease progression in perinatally human immunodeficiency virus type 1-infected children.

The effect of CC-chemokine receptor 5 (CCR5) promoter polymorphisms on the natural history of human immunodeficiency virus (HIV) disease was studied in 73 HIV-1-infected children. The CCR5(59338-59537) promoter haplotype, CCR5-59029A/G polymorphism, and CCR5Delta32 and CCR2-64I alterations were investigated. After exclusion of carriers of CCR5Delta32 or CCR2-64I, Kaplan-Meier analysis disclosed that children with the P1/P1(59353C,59356C,59402A) genotype progressed faster to disease than did children with other haplotypes (P=.016). When CCR2-64I carriers were included, this effect had borderline significance (P=.065) and was lost when CCR5Delta32 carriers were also considered (P=.387). The P1/P1 effect was strongest early after infection, when progression to disease was mainly associated with CCR5 coreceptor-using viruses. These results indicate that the P1/P1 genotype is predictive of rapid progression in HIV-1-infected children lacking CCR5Delta32 or CCR5-64I alleles. The observation of a linkage disequilibrium between P1 and 59029A might explain the previously reported association between 59029A homozygosity and rapid disease progression.

Adolescent↗

Co-receptor usage of HIV-1 primary isolates, viral burden, and CCR5 genotype in mother-to-child HIV-1 transmission.

OBJECTIVE: To investigate the relationship between CC chemokine receptor 5 (CCR5) genotype, viral load and co-receptor usage of maternal HIV-1 isolates in perinatal HIV-1 transmission. PATIENTS AND METHODS: A total of 181 mothers and infants were studied at the time of delivery. Wild-type (wt) and delta32 CCR5 alleles were determined by means of polymerase chain reaction (PCR). The viral load in maternal plasma samples was determined by a quantitative reverse transcriptase-PCR assay; co-receptor usage of maternal isolates was determined by viral infection in cells stably expressing CCR5 or CXC chemokine receptor 4 (CXCR4) co-receptors. RESULTS: HIV-1 transmission rates in wt/wt and wt/delta32 mothers (14.7 versus 15.8%), and in wt/wt and wt/delta32 infants (14.6 versus 14.3%) were similar. Mothers transmitting infection to wt/delta32 infants had significantly higher HIV-1-RNA levels than those who transmitted infection to wt/wt infants (5.4 versus 4.1 log10 copies/ml, P = 0.03). In wt/wt children there was a positive relationship between transmission rate and maternal viral load over the entire range of HIV-1 values, whereas in wt/delta32 children transmission occurred only at viral loads greater than 4.0 log10 copies/ml. Logistic regression analysis confirmed that the relationship between viral load and transmission varied according to the child's CCR5 genotype (P = 0.035; adjusted for zidovudine prophylaxis and mode of delivery, P = 0.090). Moreover, the majority of wt/wt transmitting mothers had R5-type isolates, whereas none of the wt/delta32 mothers with an R5-type virus transmitted HIV-1 to their wt/delta32 infants. CONCLUSION: Taken together, these findings suggest that CCR5 delta32 heterozygosity exerts a protective effect against perinatal transmission in children exposed to a low maternal viral burden of an R5-type isolate.

Cetirizine↗

Restriction of HIV type 1 infection in macrophages heterozygous for a deletion in the CC-chemokine receptor 5 gene.

Homozygosity for a 32-base pair deletion (delta32) within the CC-chemokine receptor 5 (CCR5) gene confers resistance to infection by R5-type HIV-1 isolates. To ascertain how CCR5delta32 heterozygosity influences the susceptibility of lymphocytes and macrophages to HIV-1 infection, peripheral blood lymphocytes (PBLs) and monocyte-derived macrophages (MDMs) from three HIV-1-uninfected CCR5delta32 heterozygous infants and three HIV-1-uninfected CCR5 wild-type homozygous infants were exposed to two R5-type primary isolates. HIV-1 infection was monitored by DNA-PCR and p24 antigen determination; CCR5 and CCR5delta32 transcripts were quantified by competitive reverse transcription-PCR. Wild-type homozygous MDMs and PBLs and heterozygous PBLs were infected by both viral isolates, albeit with different efficiencies, but heterozygous MDMs showed restriction to HIV-1 infection. Lower levels of CCR5 mRNA and protein expression were found in heterozygous versus wild-type homozygous MDMs and PBLs. Interestingly, wild-type homozygous MDMs showed higher levels of CCR5 mRNA expression compared with wild-type homozygous PBLs, while heterozygous MDMs had lower levels of CCR5 wild-type mRNA and a higher CCR5delta32/CCR5 mRNA ratio compared with heterozygous PBLs. These findings suggest that CCR5delta32 heterozygosity confers a different degree of protection against HIV-1 in PBLs and MDMs, depending on the ratio of wild-type and mutant CCR5 mRNA in the two cell types, and may delay virus spread in the host by preventing infection of monocytes and macrophages.

Adult↗

Social learning of a food preference in male and female Mongolian gerbils is facilitated by the anxiolytic, chlordiazepoxide.

Social transmission of a food preference in Mongolian gerbils (Meriones unguiculatus) depends on the presence of a social bond between the interacting animals. An "observer" gerbil can acquire a preference for a novel food item from a familiar and, or related "demonstrator" animal. However, exposure to an unfamiliar and unrelated demonstrator gerbil does not lead to acquisition of a food preference, even though the extent of social interaction and likelihood of transmission of food information is unaffected. Likewise, individual preexposure to a novel food does not affect diet preference in individual animals. Here we show that oral, nongavage, administration of the benzodiazepine anxiolytic, chlordiazcpoxide (CDP, 2.5, 5, and 10 mg/kg) has significant dose-associated differential facilitatory effects on social learning in male and female gerbils, while having no significant effects on either individual learning or total food consumption. These results suggest that the CDP mediated reduction of the anxiety associated with the interactions between unfamiliar/unrelated gerbils facilitates social learning. These findings also rise the possibility of sex differences in socially related anxiety and the effects of CDP on social learning in gerbils.

Animals↗

Comparing different forms of male and female aggression in wild and laboratory mice: an ethopharmacological study.

The purpose of this study was to compare the effects of 2 mg/kg fluprazine (a serotonergic psychoactive drug with antiaggressive properties) on intrasexual attack, infanticide, and predation (on an insect larva) in males and females of wild and Swiss mice. The results showed that, in both stocks of mice, fluprazine significantly inhibited intrasexual and infanticidal attack in both sexes, but predatory attack was not altered by the drug treatment. Motivational and neural substrates underlying intrasexual attack and infanticide appear, thus, to be related to each other, and similarly modulated in both males and females. Conversely, predatory attack seems to be under a different neurohumoral control. The similar regulation of proximal mechanisms of aggressive behavior observed in wild and Swiss mice suggests a common neurobiology of aggression. For this reason, the outbred laboratory Swiss mice appear to be a reliable model for studies on causal and functional mechanisms of aggression.

Aggression↗

Assessment of heart rate variability changes during dipyridamole infusion and dipyridamole-induced myocardial ischemia: a time variant spectral approach.

OBJECTIVES: We sought to evaluate changes in RR interval variability during dipyridamole infusion and dipyridamole-induced myocardial ischemia. BACKGROUND: Myocardial ischemia and the autonomic nervous system can be mutually interdependent. Spectral analysis of RR interval variability is a useful tool in assessing autonomic tone. METHODS: We used a time variant autoregressive spectral estimation algorithm that could extract spectral variables even in the presence of nonstationary signals. Two groups were considered: group A (patients with ischemia, n = 15) with effort or mixed angina, angiographically assessed coronary artery disease and positive exercise and dipyridamole echocardiographic test results, and group B (control subjects, n = 10) with normal exercise and dipyridamole echocardiographic test results. We investigated the following variables: RR interval mean and variance, low frequency (LF) and high frequency (HF) power in normalized units, LF ratio (LF/LFbasal power), HF ratio (HF/HFbasal power) and LF/HF ratio. For each test epoch, we calculated for group A and group B the mean value +/- SE of all indexes considered. Differences due to an effect either of group (ischemic vs. control) or of time (including both drug and ischemia effects) were analyzed by using analysis of variance for repeated measurements. RESULTS: Dipyridamole injection was characterized by a reduction of all spectral components in negative test. The LF ratio was the only variable able to discriminate patients with ischemia from control subjects (p < 0.05), whereas a time effect was evident for both mean RR interval and high frequency power in normalized units (p < 0.05). The LF ratio decreased in group B from 1 +/- 0.00 (basal) to 0.31 +/- 0.22 (peak), and increased in group A from 1 +/- 0.00 to 15.41 +/- 6.59, respectively. Results of an unpaired t test comparing the peak values of the two groups were also statistically significant (p < 0.01). CONCLUSIONS: Our data show that time variant analysis of heart rate variability evidences an increase in the low frequency ratio that allows differentiation of positive from negative test results, suggesting that the electrocardiogram may contain ischemia information unrelated to ST-T variations, even if their enhancement requires a more complex data processing procedure.

Aged↗

Kinship and familiarity as factors affecting social transfer of food preferences in adult Mongolian gerbils (Meriones unguiculatus).

Experiments were carried out with Mongolian gerbils (Meriones unguiculatus) to assess whether a socially mediated acquisition of diet selection exists in this species. Results showed that a gerbil was influenced in its diet choices by information extracted during a brief period of interaction with a familiar conspecific that had recently eaten a novel food. Data revealed that the acquisition of a food preference from a conspecific depends on the existence of a social bond between the interacting gerbils. Either genetic relatedness (being brother or sister raised in different litters) or familiarity (being bred in the same litter or being member of a reproductive pair) is necessary for the transfer of information. Unfamiliar and unrelated observer gerbils did not selectively choose their demonstrator's food.

Age Factors↗

Time-variant power spectrum analysis for the detection of transient episodes in HRV signal.

A time-variant algorithm of autoregressive (AR) identification is introduced and applied to the heart rate variability (HRV) signal. The power spectrum is calculated from the AR coefficients derived from each single RR interval considered. Time-variant AR coefficients are determined through adaptive parametric identification with a forgetting factor which obtains weighed values on a running temporal window of 50 preceding measurements. Power spectrum density (PSD) is hence obtained at each cardiac cycle, making it possible to follow the dynamics of the spectral parameters on a beat-by-beat basis. These parameters are mainly the LF (low frequency) and the HF (high frequency) powers, and their ratio LF/HF. These together account for the balanced sympatho-vagal control mechanism affecting the heart rate. This method is applied to subjects suffering from transient ischemic attacks. The time variant spectral parameters suggest an early activation of LF component in the HRV power spectrum. It precedes by approximately 1.5-2 min the tachycardia and the ST displacement, generally indicative of the onset of an ischemic episode. The results suggest an arousal of sympathetic system before the acute attack.

Algorithms↗

The inhibitory effects of fluprazine on parental aggression in female mice are dependent upon intruder sex.

Lactating resident mice respond differently to male and female intruder conspecifics, showing defensive attack towards the former and offensive attack towards the latter. The effects of fluprazine (1-5 mg/kg) on this differential response pattern have been assessed. Although fluprazine increased the latencies of attack on male intruders, a very much more potent inhibitory effect was observed on attacks directed towards female intruders. Fluprazine also modestly reduced social investigation of female intruders and increased nest-oriented behaviour irrespective of the intruder's sex. As the pattern of attack on intruders, exploration, fear responses and maintenance behaviour all remained largely intact under drug treatment, it seems unlikely that the drug's inhibitory action on attack involves fear potentiation and/or olfactory impairment. It is suggested that the greater sensitivity of offensive attack to the inhibitory actions of fluprazine may reflect the relative degree of threat to resident parental investment posed by male and female conspecific intruders.

Aggression↗

[Description of a system for automatic analysis of ambulatory electrocardiography using a microcomputer].

An automatic ambulatory electrocardiogram analyzer was developed using a self-powered fast reader of FM recorded cassettes and a "general purpose" microcomputer with 640 Kbytes of RAM and 20 Mbytes of mass memory on hard-disk. Original algorithms were developed for analog to digital conversion, data storage on hard-disk, QRS detection and classification and rhythm analysis. Reliability of the system was evaluated, when appropriate, using standard databases. The relevant features of our analyzer include a favourable cost/benefit ratio, powerful interactive facilities and the typical flexibility of the non dedicated hardware.

Algorithms↗

Serum and urine concentrations of rifampicin administered by intravenous infusion in man.

Two studies were carried out in man with the aim of assessing the serum and urine concentrations of rifampicin administered by i.v. infusion. In patients suffering from various diseases, a dose of 600 mg i.v. proved to be equieffective with a 600 mg oral dose. Repeated administration of a 600 mg dose by i.v. infusion for a week produced serum levels corresponding to those achieved by oral administration. With the i.v. preparation the drop in serum rifampicin levels during continuous administration was less marked than with the oral administration. The recovery of antibiotic in the urine seems to be lower with i.v. than with the oral preparation. The i.v. preparation was very well tolerated by all the patients.

Administration, Oral↗

Kinetics of rifampicin and isoniazid administered alone and in combination to normal subjects and patients with liver disease.

The possible existence of kinetic interactions between rifampicin and isoniazid and the effect of the concomitant presence of an impaired liver function were investigated in man. In a first study normal healthy subjects and patients with chronic liver disease received, on three different occasions, a single dose of 600 mg rifampicin or isoniazid and of rifampicin and isoniazid associated in randomized sequences. The results have shown that in both groups the serum levels, half-life values, and urinary excretion of each drug given alone are not significantly different from those observed when the other drug is associated. Serum levels and half-life of rifampicin and isoniazid were significantly higher in patients with chronically impaired liver. In a second study, rifampicin and isoniazid were given in combination at the same doses as in the first study over a period of one week. The results have shown a trend to decrease in the serum levels of rifampicin of the healthy subjects and a trend to increase in the patients with chronic liver disease on day 7 of treatment. In both groups a reduction in the half-life of rifampicin was also observed. No changes in serum isoniazid concentrations were observed between day 1 and day 7 in the healthy subjects, whereas a significant increase was observed in the patients. No significant changes in the half-life of isoniazid were observed.

Adult↗