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Biomedical subjects

Giuseppe Mirabella

Publications and source records attributed to Giuseppe Mirabella.

6 recordsLinked to original sources

Visual development in very low birth weight infants.

Extremely preterm infants are at risk for neurodevelopmental problems and the visual system is particularly vulnerable. However, development of visual function in preterm infants with little or no retinal or neurologic injury has not been well defined. This study compared development of visual function in preterm infants without severe retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL) to that of term infants at 5-7 mo corrected age. Twenty-one very low birth weight (VLBW) preterm infants (24-32 wk gestational age, weighing < 1500 g), and 22 healthy term infants were tested at 5-7 mo corrected age. Infants with any IVH/PVL and > Stage II ROP or Plus disease were excluded. Contrast sensitivity, grating acuity, and vernier acuity were measured using swept-parameter visual evoked potentials. Thresholds and maximum amplitudes were compared between groups. VLBW and term infants showed no differences in sensitivity for contrast (67.5 versus 63.8), grating resolution (12.4 versus 12.5 cpd) or vernier acuity (1.2 versus 1.0 arcmin). However, the amplitudes for swept contrast (p < 0.03) and swept vernier offset (p < 0.04) stimuli were higher in VLBW infants. Visual thresholds in VLBW infants without serious retinal or neurologic abnormalities were not significantly different from those of term infants, suggesting that increased visual experience does not influence visual sensitivity. The higher amplitudes in VLBW infants, suggests that visual experience may affect responses to suprathreshold stimuli.

Contrast Sensitivity↗

Development of contrast sensitivity in infants with prenatal and neonatal thyroid hormone insufficiencies.

Thyroid hormone is essential for normal brain development including structures critical for visual processing. While chick and rodent models have demonstrated abnormal visual development following prenatal thyroid hormone loss, comparable data do not exist in the human. To determine whether human infants with intrauterine and early postnatal thyroid hormone insufficiencies have compromised visual abilities, we investigated contrast sensitivity and visual acuity development in 13 infant offspring of women with hypothyroidism during pregnancy (HYPO), 16 preterm infants born between 32 and 35 weeks gestation, 12 infants with congenital hypothyroidism (CH), and 20 typically developing infants. All were assessed with the sweep visual evoked potential technique at 3, 4.5, and 6 months (corrected) age. Results showed significantly reduced contrast sensitivity but normal visual acuity in HYPO and CH groups relative to controls (p < 0.003 and p < 0.05 respectively). Stratification of the HYPO group into subgroups based on maternal TSH levels during the first half of pregnancy revealed lower contrast sensitivities for infants whose mothers' TSH values were above than below the median (p < 0.05). In the CH group, those with an absent thyroid gland and/or a newborn TSH value above 200 mIU/L had lower contrast sensitivities than did those with other etiologies or TSH levels below 100 mIU/L (p < 0.05). There were no significant effects involving the preterm group. These results indicate that thyroid hormone is important for human visual development.

Animals↗

Evidence for the presence of alpha1 adrenoceptor subtypes in the human ureter.

AIM: Several studies have proposed a role for alpha1 adrenoceptors (ARs) in ureteral physiology, indicating that they are present in the ureter; however, few studies have been done to identify alpha1 AR subtypes present in this area. Thus, this study was carried out to characterize the alpha1 AR subtype gene and protein expression in proximal, medial, and distal region of the human ureter. METHODS: Molecular characterization of alpha1 AR subtypes were analyzed by semi-quantitative RT-PCR. alpha1 AR protein expression was studied by saturation binding curves and by competition binding curves with selective antagonists. Analysis of data was performed using the GraphPad PRISM 4 software. RESULTS: Analysis of saturation binding curves revealed a heterogeneous distribution of alpha1 AR binding sites, the B(max) for the distal ureter was indeed 52.5 +/- 5.4 fmol/mg prot, while a lower similar density of alpha1 ARs was demonstrated in the medial (25.2 +/- 1.7 fmol/mg prot) and proximal (23.4 +/- 0.4 fmol/mg prot) ureters. Molecular and pharmacological characterization of alpha1 AR subtypes indicated that each receptor was present, although with differences in terms of the amount expressed. CONCLUSIONS: Human ureter was endowed with each alpha1 AR subtype, although alpha1D and alpha1A ARs were prevalent over alpha1B ARs. Radioligand binding results revealed that there were no significant differences in the K(d) between ureteral regions, while a heterogeneous distribution of alpha1 AR binding sites was detected, with the highest density of alpha1 ARs in the distal ureter and a lower similar density in the medial and proximal ureters.

Aged↗

Reduced visual function associated with infantile spasms in children on vigabatrin therapy.

PURPOSE: To use visual evoked potential (VEP) testing to determine whether visual deficits are present in children with a history of vigabatrin use. METHODS: Contrast sensitivity and visual acuity were assessed by visual evoked potential testing and compared between 28 children (mean age, 4.90 +/- 4.92 years) with seizure disorders who had taken vigabatrin and 14 typically developing children (mean age, 3.14 +/- 1.70 years). Exclusion criteria were heritable eye disease, suspected cortical visual impairment, nystagmus, and prematurity >2 weeks. The effects of the following factors on contrast sensitivity and visual acuity were examined: type of seizure (infantile spasms versus other), ERG result, duration of vigabatrin therapy, cumulative dosage of vigabatrin, and other seizure medications (other versus no other medication). RESULTS: Contrast sensitivity and visual acuity were reduced in vigabatrin-treated children with infantile spasms compared with vigabatrin-treated children with other seizure disorders and typically developing control subjects. The other factors examined had no significant effect on contrast sensitivity or visual acuity, with adjustment for seizure type. CONCLUSIONS: Children with infantile spasms on vigabatrin may have compromised visual function, even in the absence of suspected cortical visual impairment. The children tested in the present study have reduced vision, probably associated with infantile spasms rather than vigabatrin.

Adolescent↗

Alpha1 adrenoceptor subtypes in human urinary bladder: sex and regional comparison.

A detailed study of the presence of alpha1 AR binding sites and alpha1 AR subtype mRNA expression in human urinary bladder areas involved in the micturition (i.e. detrusor, trigone and neck) is reported here, investigating whether or not there are differences between sexes. Results obtained indicated that alpha1 AR proteins were detectable in each bladder area. In both sexes, the detrusor and the neck expressed similar levels of alpha1 ARs: respectively, detrusor: 14.6 +/- 1.2 in men and 13.1 +/- 1.1 fmol/mg prot in women; neck: 16.9 +/- 3.2 in men and 17.5 +/- 4.1 fmol/mg prot in women. In the trigone, significantly higher alpha1ARs were found in women compared to men (20.6 +/- 1.1 vs 11.7 +/- 0.7 fmol/mg prot). Subtype analysis indicated that in women, each area was endowed with mRNA encoding for each alpha1 AR subtype. The men detrusor expressed alpha1a and alpha1d ARs, while in the trigone and the neck, each subtype was present. Since the detrusor muscle hypertrophy is a marker of bladder obstructive outlet, the selective alpha1 AR subtype targeting arouses much interest, as evidence indicates that there are differences in signalling pathways among the subtypes. Furthermore, the significance of the alpha1 ARs coexpression is still unknown; interestingly, recent papers demonstrate that alpha1 AR subtypes could dimerize. Thus, in the human urinary bladder it may be suggested a potential level of alpha1 AR complexity that could have an impact on drug development.

Aged↗

Differential gene expression of cholinergic muscarinic receptor subtypes in male and female normal human urinary bladder.

OBJECTIVES: To study the mRNA expression of each muscarinic receptor subtype in bladder areas involved in micturition, such as the bladder dome, neck, and trigone. Our study focused on the analysis of the gene expression of muscarinic receptors in the human male and female urinary bladder. Other than the well-known role of bladder parasympathetic innervation, an extensive study of the muscarinic receptor mRNA distribution in male and female urinary bladder is still lacking. METHODS: The study was carried out on 5 female (age 56 +/- 10 years) and 5 male (age 70 +/- 9 years) patients. The patients selected for this study did not have any lower urinary tract symptoms, as determined by International Prostate Symptom Score questionnaire. The mRNAs encoding muscarinic receptor subtypes were assessed by reverse transcription-polymerase chain reaction, followed by Southern blot analysis. RESULTS: Using a molecular approach, we demonstrated the presence of all muscarinic receptor subtypes in the different urinary bladder areas involved in micturition; in particular, our data indicated that mRNAs encoding muscarinic receptors are largely expressed in all examined bladder areas, both in men and women, although with some remarkable differences and a peculiar distribution. CONCLUSIONS: Our results indicate that the pharmacology of the human bladder may be more complex than previously recognized. Furthermore, the choice to study each biopsy as a single sample and not use a pool of tissues allowed us to point out the individual variability between subjects and sex-related differences in the expression profile of muscarinic receptor subtype mRNAs.

Aged↗