Glicoproteína-P, resistência a múltiplas drogas (MDR) e relação estrutura-atividade de moduladores

Multidrug resistance, MDR is a major obstacle for cancer chemotherapy. MDR can be reversed by drugs that vary in their chemical structure and main biological activity. Many efforts have been done to overcome MDR based on studies of structure-activity relationships and in this review we summarize some aspects of MDR mediated by P-glycoprotein (P-gp), as the most experimentally and clinically tested form of drug resistance. The most significant MDR mechanisms revealed until now are shortly discussed. Physicochemical and structural properties of MDR modulators, measures of the MDR reversal, and QSAR studies are included.

Química forense: perspectivas sobre novos métodos analíticos aplicados à documentoscopia, balística e drogas de abuso

In this review recent methods developed and applied to solve criminal occurences related to documentoscopy, ballistic and drugs of abuse are discussed. In documentoscopy, aging of ink writings, the sequence of line crossings and counterfeiting of documents are aspects to be solved with reproducible, fast and non-destructive methods. In ballistic, the industries are currently producing ''lead-free'' or ''nontoxic'' handgun ammunitions, so new methods of gunshot residues characterization are being presented. For drugs analysis, easy ambient sonic-spray ionization mass spectrometry (EASI-MS) is shown to provide a relatively simple and selective screening tool to distinguish m-CPP and amphetamines (MDMA) tablets, cocaine and LSD.

Levotiroxina e o problema da permutabilidade de drogas de estreito intervalo terapêutico

The exchange of a prescribed drug by other similar, by generic products and even by custom products has become common practice in our country, often ignoring basic tenets of bioequivalence, interchangeability, stability and characteristics of the pharmaceutical compounds. In the case of drugs of narrow therapeutic index, such as levothyroxine, these problems are intensified, putting the effectiveness of treatment and patient health at serious risk. We review the pertinent legislation, emphasizing the characteristics of levothyroxine and adverse effects that limit the interchangeability of the compound.

Modificações morfo-funcionais do tecido muscular induzidas pela atividade excentrica : um estudo global dos processos adaptativos

Universidade Estadual de Campinas . Faculdade de Educação Física

Adaptações cardio-respiratorias induzidas pelo treinamento fisico aerobio em homens na faixa etaria de 46 a 60 anos : Estudo longitudinal e transversal

Universidade Estadual de Campinas . Faculdade de Educação Física

A pilot study of topiramate in children with Lennox-Gastaut syndrome

We conducted an open, add-on study with topiramate (TPM) as adjunctive therapy in Lennox-Gastaut syndrome (LGS), to assess the long-term efficacy and safety and to evaluate quality of life (QL) measurements in the chronic use of TPM. We studied 19 patients (11 male; age ranging from 4 to 14 years) with uncontrolled seizures receiving 2-3 anti-epileptic drugs. Patients were followed up to 36 months of treatment. A questionnaire was used to query parents about QL. Seven patients completed the study at 36 months and seizure frequency was reduced > 75% in 4, and < 50% in 3 patients. Two children became seizure free for more than 24 months. Most side effects were CNS related, with the most frequent being somnolence and anorexia. These were generally transient. One patient dropped-out due to powder in the urine. None of the patients required hospitalization. At 36 months, patients' alertness (2/7), interaction with environment (5/7), ability to perform daily activities (5/7), and verbal performance (6/7) improved on TPM. We conclude that TPM may be useful as adjunctive therapy in the treatment of LGS. The efficacy of TPM was maintained in long-term treatment in more than 40% of patients, long term safety was confirmed and QL improved on TPM.

Neurological evaluation of neonates with intraventricular and periventricular hemorrhage

We studied the clinical aspects of 100 consecutive premature newborns with and without intraventricular and periventricular hemorrhage (IPVH).The diagnosis of IPVH was obtained by ultrasonic scans of the skull during the first week of life and at the age of one month. Forty eight percent of newborns with IPVH had abnormal results, and there was a significant correlation with the neurological evaluation in 85% of the infants. The probability of normality for a child with no associated brain abnormalities was 72%, whereas for a child of the same gestational age with associated brain abnormalities was 48.7%.

Multifunctional role of steroidogenic factor 1 and disorders of sex development

Disorders of sex development (DSD) involve several conditions that result from abnormalities during gonadal determination and differentiation. Some of these disorders may manifest at birth by ambiguous genitalia; others are diagnosed only at puberty, by the delayed onset of secondary sexual characteristics. Sex determination and differentiation in humans are processes that involve the interaction of several genes such as WT1, NR5A1, NR0B1, SOX9, among others, in the testicular pathway, and WNT4, DAX1, FOXL2 and RSPO1, in the ovarian pathway. One of the major proteins in mammalian gonadal differentiation is the steroidogenic nuclear receptor factor 1 (SF1). This review will cover some of the most recent data on SF1 functional roles and findings related to mutations in its coding gene, NR5A1.

Ocular findings in Brazilian identical twins with Cohen syndrome: case report

A case of identical male twins with Cohen syndrome who present multiple ophthalmic findings is reported. The patients were identical 16 year-old twin boys who showed down slanting eyelids, mild ptosis, high-grade myopia, small cortical lens opacities, posterior subcapsular cataracts, myotic and corectopic pupils with poor dilation due to focal iris atrophy and retinochoroidal dystrophy. Ophthalmologists must be aware of the ocular and systemic findings of Cohen syndrome in the evaluation of young patients with mental retardation and visual impairment.

Assessment of ocular surface toxicity after topical instillation of nitric oxide donors

PURPOSE: To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) in a hydroxypropyl methylcellulose (HPMC) matrix at final concentrations 1.0 and 10.0 mM. METHODS: Ex vivo GSNO and SNAC toxicities were clinically and histologically analyzed using freshly excised pig eyeballs. In vivo experiments were performed with 20 albino rabbits which were randomized into 4 groups (5 animals each): Groups 1 and 2 received instillations of 150 µL of aqueous HPMC solution containing GSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4 received instillations of 150 µL of aqueous HPMC solution-containing SNAC 1.0 and 10.0 mM, respectively, in one of the eyes. The contralateral eyes in each group received aqueous HPMC as a control. All animals underwent clinical evaluation on a slit lamp and the eyes were scored according to a modified Draize eye test and were histologically analyzed. RESULTS: Pig eyeballs showed no signs of perforation, erosion, corneal opacity or other gross damage. These findings were confirmed by histological analysis. There was no difference between control and treated rabbit eyes according to the Draize eye test score in all groups (p>0.05). All formulations showed a mean score under 1 and were classified as non-irritating. There was no evidence of tissue toxicity in the histological analysis in all animals. CONCLUSION: Aqueous HPMC solutions containing GSNO and SNAC at concentrations up to 10.0 mM do not induce ocular irritation.

Neuronal Ceroid-lipofuscinosis with prominent chorea and without visual manifestations: a case report

A case of neuronal ceroid-lipofuscinosis (NCL) is reported in a 11-year-old girl, whose main symptoms were progressive dementia since the age of 4 years and choreic movements since age 10. Seizures, myoclonus and visual deterioration were absent and optic fundi were normal. A cerebral biopsy disclosed two basic types of stored substance in the cytoplasm of neurons: a) severely balloned nerve cells in cortical layers HI and V contained a non-autofluorescent material, which stained with PAS and Sudan Black B in frozen, but not in paraffin sections; ultrastructurally, these neurons showed abundant corpuscles similar to the membranous cytoplasmic bodies of Tay-Sachs disease and, in smaller amounts, also zebra bodies; b) slightly distended or non-distended neurons in all layers contained lipopigment granules, which were autofluorescent, PAS-positive and sudanophil in both frozen and paraffin sections; their ultrastructure was closely comparable to that of lipofuscin. Similar bodies were found in the swollen segments of axons and in a few astrocytes and endothelial cells. The histochemical and ultrastructural demonstration of large amounts of lipopigments allows a presumptive classification of the case as NCL. However, the presence of involuntary movements, the absence of visual disturbances and the unusual ultrastructural features place the patient into a small heterogeneous group within the NCL. A better classification of such unique instances of the disease must await elucidation of the basic enzymatic defects.

Herpes Zoster oftálmico e posterior acidente vascular cerebral: relato de caso

A sixty-nine year old man suffered a stroke fourteen weeks after the onset of right herpes zoster ophthalmicus (HZO). Hemispheric infarction was documented by a computed tomography which showed a small hypodense zone in the right internal capsula; after contrast there was enhancement of this hypodense area. Cerebral angiography and cerebral-spinal fluid were not done. Despite of a diagnosis of probability the authors report the case and review the literature. A long latency between the HZO and onset of neurological deficit is stressed. New antiviral agents may prevent the ictus.

Período ovulatório e crises epilépticas

We prospectively follow up 80 mentally healthy women at menacme age, with chronic epilepsy and had had least one seizure in the month preceding the study. We selected 59 patients from whom we were able to observe at least three regular menstrual cycles with seizures. We defined regular, irregular cycle, perimenstrual and ovulation period. According to our concepts we have got 19, 30 and 6 patients with respectively severe, moderate and mild exacerbation of perimenstrual seizures. Using our definitions 6, 20 and 17 patients showed severe, moderate and mild accentuation of seizures during ovulation, while 15 patients showed no ovulatory accentuation. Our attention was drawn to the great number of perimenstrual and ovulatory exacerbation of seizures, according to our criteria. From 55 patients with perimenstrual accentuation of seizures 44 (74.54%) showed exacerbation during the ovulatory period. In our opinion, these data speak out in favor of the hormonal theory to explain these occurrences. We discuss these data based on the avaiable literature. We think the strogen peak is probably the main cause of the increased frequency of epileptic seizures during the ovulation period. New studies, documenting objectively the ovulation and seizures are mandatory to clarify the relationship of these aspects of the female endocrine reproductive physiology in epileptics.

Familial glioblastoma

The authors describe a family with three members affected by glioblastoma. The proband patient, a 7 year-old girl, developed a rare complication, a pulmonary metastasis. Chromosomal analysis of her peripheral blood lymphocytes showed a normal karyotype (46, XX), without structural abnormalities. Cytogenetic study of the tumor cells disclosed several abnormalities: 46, XX, 7q - / 46, XX, -2, 4p-, 7p-, +15/ 46, XX. Some aspects about genetics of glial neoplasms are discussed.

Imigrantes bolivianos em São Paulo : a Praça Kantuta e o futebol

Universidade Estadual de Campinas . Faculdade de Educação Física