Biomedical subjects

Rita Greco

Publications and source records attributed to Rita Greco.

12 recordsLinked to original sources

PubMed2006

Pharmacotherapy of spasticity in children with cerebral palsy.

Spasticity is one of the most common symptoms presented by neurologic patients. Apart from surgical management, drug therapy is an important treatment of children suffering from spasticity. In this review, recent advances in the pharmacologic armamentarium are reported in detail. In particular, there are oral medications (benzodiazepines, baclofen, dantrolene sodium, alpha 2 adrenergic agonists) and parenteral medications (botulinum toxin type A and B, alcohol). Moreover, there is also baclofen that can be administered intrathecally. There are some reports supporting the use of intramuscular alcohol (45% and/or 5-7% phenol) to reduce spasticity without the loss of voluntary movement or loss of sensation. Among these drugs, intrathecal baclofen is one of the most effective substances that can reduce spasticity significantly in the upper and lower extremities. Finally, the effectiveness of therapy with botulinum toxin type A in the management of spasticity is analyzed. Botulinum toxin type A reduces hypertonia in the injected muscles for a period of 2 to 4 months without important side effects. The purpose of this article is to provide an overview of available oral and parenteral drugs for treatment of spasticity in cerebral palsy and to outline indications and contraindications.

Administration, Oral↗

PubMed2005

Endocrine and metabolic changes in epileptic patients receiving valproic acid.

It has been well known for many years that valproic acid (VPA) therapy can induce obesity and important endocrine dysfunctions; among these dysfunctions, the most common are hyperandrogenism, menstrual disorders, polycystic ovary syndrome, hyperinsulinism, and changes in LH, FSH, and sexual and thyroid hormones. Moreover, abnormalities in pubertal development and impaired skeletal growth have been reported. The aim of this review is to analyze the main effects of VPA on endocrinological functions in patients with epilepsy in order to understand in depth the pathophysiological mechanisms and, consequently, to improve the care of these patients.

Anticonvulsants↗

PubMed2004

Catalytic domain crystal structure of protein kinase C-theta (PKCtheta).

A member of the novel protein kinase C (PKC) subfamily, PKC, is an essential component of the T cell synapse and is required for optimal T cell activation and interleukin-2 production. Selective involvement of PKC in TCR signaling makes this enzyme an attractive therapeutic target in T cell-mediated disease processes. In this report we describe the crystal structure of the catalytic domain of PKC at 2.0-A resolution. Human recombinant PKC kinase domain was expressed in bacteria as catalytically active phosphorylated enzyme and co-crystallized with its subnanomolar, ATP site inhibitor staurosporine. The structure follows the classic bilobal kinase fold and shows the enzyme in its active conformation and phosphorylated state. Inhibitory interactions between conserved features of staurosporine and the ATP-binding cleft are accompanied by closing of the glycine-rich loop, which also maintains an inhibitory arrangement by blocking the phosphate recognition subsite. The two major phosphorylation sites, Thr-538 in the activation loop and Ser-695 in the hydrophobic motif, are both occupied in the structure, playing key roles in stabilizing active conformation of the enzyme and indicative of PKC autocatalytic phosphorylation and activation during bacterial expression. The PKC-staurosporine complex represents the first kinase domain crystal structure of any PKC isotypes to be determined and as such should provide valuable insight into PKC specificity and into rational drug design strategies for PKC selective leads.

Amino Acid Sequence↗

PubMed2004

Obesity and plasma concentrations of alpha-tocopherol and beta-carotene in epileptic girls treated with valproate.

To investigate whether epileptic patients who become obese after valproic acid (VPA) therapy can have a high risk of atherosclerosis related to the oxidation of low-density lipoprotein, we prospectively studied the plasma concentrations of lipid-soluble antioxidant vitamins in a group of 20 epileptic girls and 20 controls. After 1 year of VPA treatment, epileptic patients who gained weight had decreased plasma concentrations of alpha-tocopherol and alpha- and beta-carotene, the main lipid-soluble antioxidants. Moreover, 5 patients who gained weight were reevaluated 6 months after withdrawal from VPA therapy and showed normal body mass indices and normalized plasma levels of antioxidants. In conclusion, the data suggest that epileptic patients who gain weight after VPA therapy have reduced plasma concentrations of antioxidant vitamins and that these reductions are reversible after VPA withdrawal.

Adolescent↗

PubMed2004

Interferon-gamma cooperates with Helicobacter pylori to induce iNOS-related apoptosis in AGS gastric adenocarcinoma cells.

Helicobacter pylori colonizes the human stomach and causes gastric disease. The resulting gastric damage is a multi-step process involving several molecular factors and different target cells. Th1 cytokines released by neutrophils and lymphoid cells that infiltrate gastric mucosa, nitric oxide production and inducible nitric oxide synthase (iNOS) are associated with immune activation and tissue injury. Many other molecular processes such as apoptosis, as well as angiogenic factors and integrins, are involved in H. pylori pathogenesis. We used cancer gastric cells AGS and MKN as experimental models to evaluate apoptotic rates, iNOS gene expression with and without the presence of interferon-gamma (IFN-gamma), placenta growth factor gene expression and alphav modulation. Our results show that AGS cells stimulated with H. pylori underwent apoptosis. Moreover, the addition of IFN-gamma caused a further increase in iNOS gene expression and in the apoptotic rates. We also found early modulation in PlGF and alphav expression, and noted that p53 and bax gene expression was involved in the apoptotic process. Taken together, these findings demonstrate that H. pylori employs a series of mechanisms to avoid the host defense and cause gastric mucosa damage. One H. pylori pathogenic mechanism for causing gastric damage is the induction of iNOS-dependent apoptosis that is strongly enhanced by IFN-gamma. Thus, data obtained indicate that Th1 cytokines such as IFN-gamma, via modulation of iNOS gene expression, may contribute to an increase in the pathogenicity of H. pylori infections.

Apoptosis↗

PubMed2003

von Willebrand factor and its propeptide in children with diabetes. Relation between endothelial dysfunction and microalbuminuria.

It has been shown that patients with insulin-dependent diabetes mellitus have elevated von Willebrand factor (vWF) plasma concentrations. Plasma fibrinogen, vWF, and its propeptide concentrations have been evaluated in 102 children with insulin-dependent diabetes mellitus to determine whether an increase of vWF and its propeptide levels precedes and may predict the development of persistent microalbuminuria. The patients have been divided into two groups according to the presence or absence of microalbuminuria at the end of follow-up. They have been followed up for at least 8 y. Control group consisted of 80 age- and sex-matched healthy volunteers. At the beginning of the study there was no significant difference in fibrinogen, vWF, and its propeptide levels between patients and control subjects. During the follow-up, a significant increase of plasma vWF and its propeptide has been observed in the group of patients who later developed microalbuminuria but not in those who remained normoalbuminuric. This increase started 3 y and become statistically significant (p < 0.01) 2 y before the onset of microalbuminuria, persisting until the end of the study. During the entire follow-up plasma values of fibrinogen persisted in the normal range. In conclusion, an increase in plasma concentration of vWF and its propeptide precedes microalbuminuria and, therefore, can be useful to identify children with insulin-dependent diabetes mellitus at risk to develop incipient nephropathy later in life.

Albuminuria↗

PubMed2003

Quinine sulfate and HSV replication.

Although antimalarial drugs have been developed primarily to treat malaria, they are also beneficial for many dermatological, immunological, and rheumatological diseases, for which they are mostly used today in the Western world. The aim of the present study was to investigate the effect of quinine sulfate (QS) on the multiplication and adsorption of herpes virus type I (HSV-1). When Vero cells (African green monkey kidney) are infected with HSV-1 in the presence of QS, the viral adsorption is reduced, as demonstrated by a decrease of the number of microscopic plaques of the virus. When the virus-infected Vero cells are incubated in the presence of QS, the multiplication of HSV-1 is also reduced, and the diameter of the plaque are visibly smaller. The practical implications of the antiviral action of antimalarial drugs might be especially important to immunosuppressed patients who receive these drugs for autoimmune collagen-vascular diseases or as additional therapy for AIDS.

Animals↗

PubMed2002

Quinine sulfate and bacterial invasion.

BACKGROUND: As many patients who receive antimalarial drugs for treatment of noninfectious, inflammatory diseases are also immunosuppressed and might have a concomitant bacterial infection, we studied the effectiveness of these drugs against bacterial infections, to find out whether they could protect against (and even treat) such conditions and obviate the need for an additional antibiotic drug. METHODS: Effect of QS on bacterial growth: Escherichia coli (E. coli) HB101 pRI203 were cultured overnight at 37 degrees C in TSB and inoculated (approx 1 x 10(7) cells/ml) in MEM in the presence of QS at various concentrations (0, 50 and 100 microM).The effect of QS at concentration of 50 and 100 microM on the entry process of E. coli HB101 pRI203 into HeLa cells was studied under different experimental conditions: 1. QS was incubated with 3 x 10(5) HeLa cells for 60 min at 37 degrees C prior to infection. 2. QS was added to HeLa cell monolayers during the infection period. RESULTS: QS showed no antibacterial activity after 24 h of incubation. The invasive efficiency of the bacteria was significantly inhibited at a dose-dependent manner, when QS was added to HeLa cells for 60 min at 37 degrees C prior to infection (condition 1), and to a lesser extent when added during the period of infection (condition 2). CONCLUSIONS: Although the antimalarials are generally regarded as being inactive against most extracellular bacterial species, our results indicate that QS significantly inhibited the internalization/invasion efficacy of E. coli in the host cells.

Journal Article↗

PubMed2002

Increased bone turnover in prepubertal, pubertal, and postpubertal patients receiving carbamazepine.

PURPOSE: To study the markers of bone turnover in epilepsy patients in the different stages of the pubertal growth before and after the beginning of carbamazepine (CBZ) monotherapy. METHODS: We have investigated bone turnover in 60 epilepsy patients treated with CBZ. They were stratified according to pubertal stage and compared with a control group of 60 sex- and age-matched healthy children. RESULTS: After 2 years of therapy, we found higher values of the serum markers of bone formation [bone alkaline phosphatase (bone ALP), osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP)], and of bone resorption [carboxy-terminal telopeptide of type I collagen (ICTP) and the urinary cross-linked N-telopeptides of type I collagen (NTX)] in patients than in control subjects, in presence of a normal vitamin D metabolism. CONCLUSIONS: CBZ induces an increase of bone formation and of bone resorption that seems to be independent of the pubertal stage.

Adolescent↗

PubMed2002

Anti-invasive activity of bovine lactoferrin towards group A streptococci.

Group A streptococci (GAS) are able to invade cultured epithelial and endothelial cells without evidence of intracellular replication. GAS, like other facultative intracellular bacterial pathogens, evolved such ability to enter and to survive within host cells avoiding the host defences, and bacterial intracellular survival could explain the recurrence of infections. We report here that 1 mg bovine lactoferrin (bLf)/mL significantly hindered the in vitro invasion of cultured epithelial cells by GAS isolated from patients suffering from pharyngitis and completely inhibited the invasiveness of GAS pretreated with subinhibiting concentrations of erythromycin or ampicillin. One milligram of bLf per millilitre was also able to increase the number of epithelial cells undergoing apoptosis following GAS invasion, although the number of intracellular GAS in the presence of bLf decreased by about 10-fold. The ability of bLf to decrease GAS invasion was confirmed by an in vivo trial carried out on 12 children suffering from pharyngitis and already scheduled for tonsillectomy. In tonsil specimens from children treated for 15 days before tonsillectomy with both oral erythromycin (500 mg t.i.d. (three times daily)) and bLf gargles (100 mg t.i.d.), a lower number of intracellular GAS was found in comparison with that retrieved in tonsil specimens from children treated with erythromycin alone (500 mg t.i.d.).

Animals↗

PubMed2002

Cytokine pattern in blister fluid and sera of patients with pemphigus.

BACKGROUND: Pemphigus is a chronic auto-immune blistering disease with four main variants, i.e. pemphigus vulgaris (PV), foliaceus (PF), erythematosus (PE) and vegetans. The common histological feature of this disease is acantholysis. OBJECTIVE: The aim of this study was to compare levels of some cytokines in blister fluid and sera of patients with pemphigus, using as control blister fluid of patients with bullous pemphigoid (BP) and bullous contact dermatitis (BCD). METHODS: Using an immuno-enzymatic assay (ELISA), we tested 16 sera and 6 blister fluids of patients with various forms of pemphigus (13 with PV, 1 with PF, 2 with PE), the sera of 16 healthy control subjects, 5 blister fluids of patients with BP and 5 blister fluids of patients with BCD, for the presence of some cytokines (IL-10, IL-8 and IFN-gamma). Intercellular antibodies were searched for and titred; desmoglein 1 and 3 antibody levels were independently evaluated to compare them with the severity of both cutaneous and oral involvement. RESULTS: The levels of IL-10 in the sera of patients with pemphigus were below the detection limits. IL-8 was significantly increased only in 4 samples of sera from pemphigus patients compared with controls, while IFN-gamma was detected at low levels in almost all patients compared with sera of controls. The cytokine levels in blister fluid of patients with pemphigus were significantly higher than in the sera. There was a difference between the expression of cytokines in blister fluid of control patients with BP and BCD compared with those of pemphigus patients. CONCLUSION: This report discusses the anti-inflammatory role played by IL-10 in the chronic form of pemphigus and the hypothesis of a possible role of IL-8 in neutrophil and lymphocyte-monocyte recruitment.

Adolescent↗

PubMedDate not supplied

Quinine sulfate inhibits invasion of Salmonella typhimurium and Shigella flexneri: a preliminary study.

BACKGROUND: The incidence of typhoid fever and shigellosis parallels that of malaria, so many individuals who are on antimalarial drugs can be found in areas where these diseases are widespread. We investigated the effect of quinine sulfate on the growth and invasion of Salmonella typhimurium and Shigella flexneri M90T to determine whether people on antimalarials can have secondary gain from some protection against typhoid fever and shigellosis. METHODS: The effect of 50 and 100 microM quinine sulfate on the invasive ability of Salmonella typhimurium and Shigella flexneri M90T into human colon adenocarcinoma-2 (Caco-2) cells was studied during the infection period. The invasive efficiency was expressed as the number of viable internalized bacteria by counting the colony-forming units. RESULTS: The invasive ability of Salmonella typhimurium and Shigella flexneri M90T was significantly inhibited by 50 and 100 microM quinine sulfate in a dose-dependent manner (for Salmonella typhimurium) when the drug was added to Caco-2 cell monolayers during the infection period. CONCLUSIONS: Since so many people who are on antimalarial drugs visit and inhabit areas that are endemic to typhoid fever and Shigella infection, a study on the influence of these drugs on the disease is long overdue. Our data indicate that quinine sulfate interferes with the invasion and internalization of Salmonella typhimurium and Shigella flexneri M90T into host cells. Further studies on additional strains/serotypes with other newer antimalarials at various concentrations are needed to verify this effect of quinine sulfate and to draw conclusions on its significance in vivo.

Antimalarials↗