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Biomedical subjects

T Rossi

Publications and source records attributed to T Rossi.

At least 19 recordsLinked to original sources

Simultaneous cycle sequencing assessment of (TG)m and Tn tract length in CFTR gene.

The lengths of the dinucleotide (TG)m and mononucleotide Tn repeats, both located at the intron 8/exon 9 splice acceptor site of the cystic fibrosis transmembrane conductance regulator (CFTR) gene whose mutations cause cysticfibrosis (CF), have been shown to influence the skipping of exon 9 in CFTR mRNA. This exon 9-skipped mRNA encodes a nonfunctional protein and is associated with various clinical manifestations in CF As a result of growing interest in these repeats, several assessment methods have been developed, most of which are, however, cumbersome, multi-step, and time consuming. Here, we describe a rapid methodfor the simultaneous assessment of the lengths of both (TG)m and Tn repeats, based on a nonradioactive cycle sequencing procedure that can be performed even without DNA extraction. This method determines the lengths of the (TG)m and Tn tracts of both alleles, which in our samples ranged from TG8 to TG12 in the presence of T5, T7, and T9 alleles, and also fully assesses the aplotypes. In addition, the repeats in the majority of these samples can be assessed by single-strand sequencing, with no need to sequence the other strand, thereby saving a considerable amount of time and effort.

Alleles↗

Eradication of methicillin-resistant Staphylococcus aureus from a health center ward and associated nursing home.

BACKGROUND: Long-term health care facilities have been recognized as reservoirs of multiresistant bacterial strains, especially methicillin-resistant Staphylococcus aureus (MRSA). Efforts to control MRSA in this setting usually have been only partially effective. We describe herein the eradication of epidemic MRSA from a Finnish health care center ward and affiliated nursing home. METHODS: The methods to control MRSA included (1) contact isolation precautions, (2) screening for asymptomatic carriage, (3) eradication of carriage, and (4) education of staff on hygienic measures. The first 6 patients with MRSA-positive findings were referred without delay to the Infectious Diseases Unit of the adjacent university hospital for eradication treatment. Later, an isolation unit of 6 rooms was founded in the health care center, where the MRSA-colonized patients were nursed as a separate cohort until they, in succession, were referred to the Infectious Diseases Unit for decolonization. RESULTS: From May 20 through August 17, 1993, the epidemic MRSA strain was isolated from 8 long-term patients on the 40-bed ward of the health care center, 4 of the 59 residents of the nursing home, and 1 member of the staff. Eradication of carriage was successful in all except 1 patient with dementia, who was nursed in contact isolation in the health care center until his death 21 months later. CONCLUSIONS: It is possible to eradicate MRSA from a long-term health care facility even after 13 cases by applying strict control measures. Our experience may be valuable in the future decision-making process for control of new and more challenging multiresistant bacteria, eg, vancomycin-resistant strains of MRSA.

Aged↗

A new objective method for scoring human sperm hyperactivation based on head axis angle deviation.

The aims of the present study were, first to develop a new method for evaluating sperm hyperactivation (HA) based on sperm head axis angle deviation, and second to apply this method in scoring selected sperm populations during capacitation. This was made possible by improving our original superimposed image analysis system (SIAS). The new option on the system enables us to determine the real angular deviation of the entire head in successive superimposed frames. The entire procedure for each spermatozoon requires 10-20 sec, according to the frame/rate utilized. A clear cut-off between the values of hyperactivated, transitional and non-hyperactivated spermatozoa was found at 11 and 21 frames/sec. However, at 6 frames/sec, a partial overlap between the three classes was found. We defined sperm activity as follows. At 11 frames/sec, hyperactivated: angle sum > or = 405 degrees; transitional: 200 degrees < or = angle sum < 405 degrees. At 21 frames/sec, hyperactivated: angle sum > or = 760 degrees; transitional: 350 degrees < or = angle sum < 760 degrees. The results, in agreement with previous research, show the peaks of activity at 3 h, dropping to a minimum at 6 h. This phenomenon was significantly more evident in fertile compared with subfertile semen samples.

Humans↗

Synthesis and antiproliferative activity of some benzimidazole-4,7-dione derivatives.

A series of benzimidazole-4,7-diones bearing at the 2-position the thiomethyl group or the 2-pyridyl moiety has been synthesized and tested in vitro on three tumor cell lines. Two of them show a very good antiproliferative effect. Compounds 1 and 2d are more active or equiactive, respectively, than MMC against human lymphoblastic leukemia. Both compounds exhibit high activity on human non-Hodgkin lymphoma. Compound 1 is non toxic at all the concentrations used in the antiproliferative assay and 2d is toxic only at high concentration.

Antibiotics, Antineoplastic↗

Solid-phase/solution-phase combinatorial synthesis of neuroimmunophilin ligands.

A novel solid-phase/solution-phase strategy for the synthesis of neuroimmunophilin ligands based on GPI 1046 was developed. The synthesis employs a solid-phase esterification strategy followed by a solution-phase pyruvic amide formation to produce multi-milligram quantities of discrete compounds for assay. The protocol was applied to a production library of 880 discrete compounds. A highlight of the strategy is an aqueous extractive purification of the final compounds using a novel liquid/ice extraction system developed for high throughput.

Combinatorial Chemistry Techniques↗

Effects of sildenafil (Viagra) administration on seminal parameters and post-ejaculatory refractory time in normal males.

Sildenafil is a specific inhibitor of phosphodiesterase (PDE) type 5 and represents a powerful therapy for male erectile dysfunction (ED) of different aetiology. Recently, sildenafil has been shown to restore erections in temporary ED related to the need of semen collection for assisted reproductive techniques. In this study, we investigated whether sildenafil administration modifies seminal parameters and/or erectile function in normal healthy volunteers. In a double-blind, randomized, placebo-controlled, cross-over two period investigation we enrolled 20 healthy male volunteers (mean +/- SE age 32 +/- 0.5 years). Subjects were not using any medication for the 3 month period prior to the study and were engaged in a stable relationship with proven fertility. The effects of sildenafil (100 mg) on seminal parameters and erectile function after audiovisual sexual stimulation were evaluated by semen analysis and by colour-Duplex ultrasound (the Resistive Index) respectively. In all subjects, sildenafil caused no changes in seminal and erection parameters when compared to placebo. Interestingly, sildenafil administration led to a marked reduction of the post-ejaculatory refractory time (10.8 +/- 0.9 min versus 2.6 +/- 0.7 min for placebo and sildenafil respectively; P < 0.0001). These results indicate that in normal subjects acute sildenafil treatment does not modify semen characteristics and has a positive influence over the resumption of erections following ejaculation in the presence of a continuous erotic stimulus.

3',5'-Cyclic-GMP Phosphodiesterases↗

Polymer-supported silyl cyanide and silyl azide: useful reagents for solid-phase applications.

The support of a delicate reagent on a solid matrix allows for better and safer handling of the reagent itself. Because we had an interest in silicon-based supported reagents(1) we turned our attention to a polymer-supported trialkylsilyl cyanide and trialkylsilyl azide starting from a commercially available trialkylsilane resin. The supported cyanide was obtained with excellent yield and proved to be shelf-stable. This supported reagent was reacted with a series of aldehydes and ketones yielding the corresponding polymer-supported cyanohydrins in good-to-excellent yields. A stability study on a model cyanohydrin demonstrated that these supported intermediates also can be stored for a prolonged time. For the last step, a cleavage strategy that could release either cyanohydrins or alpha-hydroxy esters was adopted. Finally, we prepared a polymer-supported trialkylsilyl azide, which also proved to be shelf-stable.

Aldehydes↗

Azoospermia: incidence, and biochemical evaluation of seminal plasma by the differential pH method.

BACKGROUND: Recent artificial reproductive technologies (ART) have enabled even azoospermic subjects to take part in "in vitro fertilization" programs. The aim of the present study was: a) to evaluate the incidence of azoospermic male partners of infertile couples; b) to determine whether biochemical evaluation of such azoospermic males can help to discriminate between obstructive and secretory azoospermia. METHODS: Semen samples (n. 28,339; period 1990-1997) were analyzed according to WHO guidelines. In addition, in 108 azoospermic subjects, fructose, citric acid and L-carnitine (taken respectively as markers of seminal vesicle, prostate and epididymal function) were assayed using a new, faster technique, the differential pH method. RESULTS: The incidence of azoospermic semen samples was 4.76%. The biochemical analyses were indicative diagnostically, especially with regard to obstructive azoospermia. However, in secretory azoospermia, biochemical analysis of seminal plasma did not offer particularly helpful indications, except in cases of hypogonadism. CONCLUSIONS: Azoospermia accounts for a relatively high number of cases and justifies detailed attention to the diagnostic and therapeutic approach. Biochemical analysis of the seminal markers is a valid support for differential diagnosis between secretory obstructive azoospermia. It can therefore help in the correct recruitment of such patients for ART programs.

Biochemistry↗

[Perinatal morbidity and mortality in children born to mothers with gestational hypertension].

Gestational hypertension is a severe pathology leading to important maternal and neonatal effects. It represents one of the most important causes of maternal morbidity and contributes to a high percentage of perinatal mortality, determined by fetal hypoxia and especially by prematurity and low birth weight. To-date the only treatment offered in gestational hypertension remains delivery, which has to be scheduled regarding timing and method on the basis of the appearance of hypertension, of its severeness and maternal and fetal complications. To evaluate the clinical course and the presence of hypertensive risk factors, a clinical-epidemiological study was carried out on two groups of pregnant women: a group made up of 50 women with hypertension and a control group of 80 women in whom no gravidic pathology arose. We hence were able to reveal the risk factors associated with hypertension in pregnancy such as maternal age, nulliparity, and elevated body mass index. Regarding neonatal prognosis, we observed a higher incidence in premature birth (30th- to 38th week of gestational age) and the need for elective or urgent caesarean sections, with respect to the spontaneous deliveries observed in the control group. We also observed reduced weight of both placenta and the newborn in hypertensive mothers with significant statistical differences between the two groups (p < 0.001). Evaluation of neonatal data at birth showed lower Apgar indices at 1st and 5th minute from birth in the study group with a higher percentage of newborns transferred to the neonatal intensive care unit. We also observed a high percentage of still-births equal to 14% in the study group as opposed to the control group.

Adult↗

[Evaluation of the peripartum effects of 2 analgesics: meperidine and tramadol, used in labor].

The need for analgesia to overcome pain in labour is highly requested by women today. Various ways either non pharmachologic e.g. Emotional sustain, psycho-prophylactic preparation, yoga and hypnosis or pharmachologic such as epidural blockade or parenteral are used. Therefore in our study we evaluated the efficacy and tolerability of the two opioids usually used today in parenteral analgesia to reduce pain during labour: Tramadol and Meperidine. We studied two groups of patients each made up of 20 women in labour, all at term and with a physiologic course of pregnancy. 75 mg i.m. of Meperidine chloryhydrate were somministered in the first group while in the second group 100 mg i.m. of tramadol chloryhydrate were somministered. Various maternal, fetal and neonatal parameters were then monitored demonstrating--A moderate maternal analgesic effect in both drugs (evaluated through the analogic grading of pain). In the group to whom Meperidine was given, sedative effects on the mother were observed associated with respiratory depression in the newborn (the latter evaluated through the Apgar index at 1st and 5th minute of life and pH of the blood obtained at the umbilical cord. The data obtained permitted us to conclude that Tramadol in accordance to the obtained in literature gives an analogous analgesic effect, with better tolerability for the absence of collateral effects on the mother, fetus and newborn.

Analgesia, Obstetrical↗

[Lavage of the birth canal with chlorhexidine: a new valid method for the prevention of perinatal infections].

Perinatal morbidity and mortality are due to various infective agents, mainly represented by beta-hemolytic group B Streptococcus. The perinatal disease related to this infection is distinguished in Early-onset, characterised by pneumonia and sepsis, and Late-onset which leads to sepsis, meningitis and pneumonia. Various strategies were therefore proposed to prevent transmission including immunisation and chemoprophylaxis. All these methods however present adverse effects and are most of all expensive to carry out. Taha et al. reported an interesting experience regarding the reduction of perinatal infections following the cleansing of the birth canal with a solution of Chlorhexidine 0.25% during labour (1996-1997). It seemed interesting for us to assess the applicability and efficacy of a new strategy of prophylaxis of perinatal infections in a Developing Country based on the association of two of the simple strategies proposed i.e.: cleansing the birth canal with chlorhexidine and chemoprophylaxis in cases with risk factors without culture screening. We studied two groups of patients: one in which cleansing of the birth canal was used and the second (control group) in which the old method already applied in the hospital (i.e. cleansing of the external genitals with Cetrimide 1%+ Chlorhexidine 0.1%) was carried out associated with antibiotic therapy when risk factors arose. We observed a total absence of neonatal mortality due to sepsis resulting from the association of the methods suggested even though the presence of sepsis evaluated through signs and symptoms like fever, poor feeding, apnoea or dyspnoea in newborns was similar in both groups.

Chlorhexidine↗

Analogues of 4,5-bis(3,5-dichlorophenyl)-2-trifluoromethyl-1H-imidazole as potential antibacterial agents.

A preliminary exploration of analogues of 4,5-bis(3,5-dichlorophenyl)-2-trifluoromethyl-1H-imidazole, 1, as novel antibacterial agents was carried out to determine the basic features of the structure responsible for the observed biological activity. The presence of two aryl rings, the imidazole NH and either a good electron withdrawing group or an aldehyde or amino group at C-2 were required for good levels of activity against methicillin resistant Staphylococcus aureus (MRSA).

Anti-Bacterial Agents↗

Application of the upgraded image superimposition system (SIAS) to the assessment of sperm kinematics.

Dedicated software for semiautomatic objective motility assessment, based on image superimposition (SIAS), was upgraded in order to allow automatic reading of sperm tracks whilst keeping the advantages of visual check instead of the digital images of classic computer-aided sperm analysis (CASA) systems. The new system is very fast and accurate and allows an excellent reading of sperm motility in standard semen analysis. Moreover, using this system, an attempt was made to define numerically straight-line velocity (VSL), curvilinear velocity (VCL) and linearity (LIN) in each WHO sperm motility class. At 21 frames sec-1, ROC curves analysis determined the following: Class 1 (typical of WHO grade 'a'): VSL > or = 23 microns sec-1 and LIN > or = 0.58; class 2 (typical of WHO grade 'b'): VSL > 10 and < 23 microns sec-1 and LIN > or = 0.58; class 3: VSL > 10 microns sec-1 and LIN < 0.58 (this additional class was added to differentiate nonstraight progressive motility from classes 1 and 2); class 4 (typical of WHO grade 'c'): VSL < or = 10 microns sec-1. The numerical definition of sperm motility classes may contribute towards standardization in the objective evaluation of sperm kinematics.

Humans↗

Correlation between high intake of glycyrrhizin and myolysis of the papillary muscles: an experimental in vivo study.

The ingestion of large quantities of glycyrrhizin, whether as a drug or a sweetener, is known, in susceptible subjects, to induce a syndrome similar to hypermineralcorticoidism, with bouts of hypertension, hypokaliaemia and rabdomyolysis, sometimes associated with severe renal failure and hypokaliaemia-induced arrythmias. Glycyrrhizin is also known to isomerize into the glycyrrhetic (or glycyrrhetinic) acids 18alpha- and 18beta-. In previous works, we reported that these metabolites cause bouts of hypertension and reduction in diuresis at low doses in the rat. In particular, the alpha isomer causes significant elimination of the calcium ion in the urine. The present findings confirm that 18alpha-glycyrrhetic acid is more toxic than either glycyrrhizin or the beta isomer. Histopathological study of tissue samples taken from rats treated with the alpha isomer also reveal selective damage to the myocardium with oedema, myolysis, apoptosis and blistering of the sarcoplasm. These effects begin to appear in the course of subchronic treatment, they manifest themselves in acute treatment and correlate closely with the electrocardiographic changes recorded in rats acutely treated with 18alpha-glycyrrhetic acid.

Animals↗

[Intra-spermatic L-carnitine and survival of sperm motility].

BACKGROUND: The aim of this work was to evaluate the intrasperm carnitine (L-C) content related to sperm motility survival in bovine cervical mucus and in culture medium (Tyrode solution). METHODS: The following subjects were selected: 15 fertile normospermic subjects (according to WHO guidelines) and 31 male partners of infertile couples (semen profile: volume > 2.0 ml; concentration > 20 x 10(6)/ml, progressive motility > or = 25% (WHO categories "a" and "b") after fluidification, abnormal forms < 70%; round cells < 1.0 x 10(6)/ml). After standard semen analysis, the samples were subdivided into three aliquots in order to carry out: a) intrasperm L-C (free, total and acetylated) assay; b) sperm motility survival in bovine cervical mucus; c) sperm motility survival in culture medium. RESULTS: A strict correlation was found between L-C (total and acetylated) content and motility survival in cervical mucus. This is probably due to the fact that in cervical mucus lipids are an important energy source for sperm and to metabolize these lipids intrasperm L-C is essential. Therefore, L-C content can be considered as an indicator of sperm motility life-span in cervical mucus. A significant correlation, even if reduced compared with cervical mucus, was also observed between L-C (total and acetylated) content and sperm motility survival in the biological medium. This probably is because the L-C system modulates the reserves of free CoA, essential to the tricarboxylic acid cycle function. CONCLUSIONS: The intrasperm L-C deficit could be due to; a) alterations in the L-C uptake mechanisms in the epididimys due to inflammatory processes; b) lack of testosterone (L-C uptake is androgen-dependent). Therefore, the therapeutic implication of this finding is that where hypomotility is due to intrasperm L-C deficit, exogenous L-C administration or improvement of L-C epididymal testosterone-dependent uptake could promote the acquisition of sperm motility.

Animals↗

Semen analysis and seminal plasma biochemistry in two brothers with familial reciprocal translocation 46,XY,t(8;9)(p10;p10) transmitted by the father.

Here we report familial balanced translocation (46,XY,t(8;9)(p10;p10) inherited by two brothers from the father. The first subject, 33 years old, was examined after 3 years of childless marriage. Semen analysis showed severe oligozoospermia, hypomotility and teratozoospermia. His brother, 29 years old, volunteered to join this study. He had not yet tried to start a family. Semen analysis showed dyspermia, but the condition was much less serious than his brother's. In both subjects, the secretory function of the epididymis and the genital tract accessory glands did not seem to be affected by this particular translocation. This case report highlights the importance of cytogenetic analysis in dealing with infertile patients suffering from severe dyspermia apparently sine causa. This is particularly the case when certain Assisted Reproductive Technology (ART) programs are recommended, where natural selection of the sperm no longer takes place (e.g. ICSI). The possible risk of an increase in fetal chromosomal abnormalities would suggest genetic counselling in all such situations.

Adult↗

Growth of preterm infants with cystic periventricular leukomalacia.

Etiology of the high rates of growth failure in children with cerebral palsy (CP) remains unclear. The purpose of this study was to evaluate the relation between growth failure in preterm infants with cystic periventricular leukomalacia (CPVL) and neonatal health complications. The population consisted of all preterm infants (51) with a gestational age of <33 weeks who were admitted to the Children's Hospital of Buffalo from 1988 to 1993 and who had CPVL. Out of the 41 survivors with CPVL who were followed, 39 developed CP and 18 developed growth failure during infancy. At the time of greatest growth failure, the majority (72%) of infants had signs of undernutrition as defined by the Waterlow (1972) classification. Oral feeding impairment was the sole risk factor for the occurrence of growth failure. Undernutrition appears to be important in the occurrence of growth failure in preterm infants with CPVL and CP.

Anthropometry↗