Striatal L-dopa metabolism studied in vivo in rats with nigrostriatal lesions

Summary We have used cerebral dialysis to monitor striatal metabolism of exogenously administered L-dopa (L-dihydroxyphenylalanine) in rats with unilateral lesions of the substantia nigra. The concentration of extracellular dopamine (DA) increased in both striata following L-dopa administration but the increase was markedly attenuated in the lesioned striatum. The formation of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the major DA metabolites, was also reduced in the lesioned striata following L-dopa administration; however, the reduction was not as great as was that of DA formation. A significant metabolism of exogenous L-dopa to 3-O-methyldopa occurred in both striata. L-dopa administration transiently increased extracellular levels of 5-hydroxyindoleacetic acid (5 HIAA) in both the lesioned and intract striata.These results suggest that the striatum with a reduction in DA nerve terminals is deficient both in the capacity to synthesize DA and in the storage mechanisms necessary to protect the newly synthesized DA from oxidative metabolism.     

Delayed haemolytic activity by the freshwater puffer Tetraodon sp. toxin.

In order to elucidate the toxin composition of the freshwater puffer in Bangladesh, about 230 specimens of Tetraodon sp. were collected from 1997 to 1999 and extracted. After partitioning the toxins between an aqueous layer and a 1-butanol layer, the toxin in the aqueous layer was characterized as paralytic shellfish poison (PSP) (data not shown), while the toxin in the 1-butanol layer was identified as palytoxin (PTX) or PTX-like substance based on the delayed haemolytic activity which was inhibited by an anti-PTX antibody and ouabain (g-strophanthin). This is the first report on the occurrence of PTX or PTX-like substance(s) in puffer fish.     

Cytogenetic damage and occupational exposure. I. Exposure to stone dust.

Cytogenetic investigations were carried out on 50 workers exposed to stone dust in a stone crusher industry and on 25 control subjects never exposed to such dust. The frequency of chromosomal aberrations and sister chromatid exchanges in exposed individuals was significantly higher than that in controls (P less than 0.01). The cytogenetic indices demonstrated a clear dependence on the working environment. The effect of smoking and/or alcoholic habits coupled with exposure to stone dust has also been investigated. The results indicate that the mutagenic risk in the working environment is probably associated with silica dust in the area.     

L-threodops increases extracellular norepinephrine levels in the brain: an in vivo study

Extracellular norepinephrine levels in the striatum of normal rats increased significantly following the administration of L-threodops. When peripheral decarboxylase activity was inhibited with carbidopa, administration of the same dose of L-threodops induced a 2.5-fold greater increase in norepinephrine levels.     

Impairment of human sperm motility and viability by quercetin is independent of lipid peroxidation

Human sperm motility, viability and lipid peroxidation were assessed in Ringer-Tyrode supplemented with different concentrations of quercetin. An irreversible and dose-dependent fall in sperm motility was observed with quercetin (5-200 microm). However, sperm viability was decreased only at higher concentrations (50-100 microm) of quercetin. This inhibition in sperm motility and viability has been linked with decreased Ca2+-ATPase activity, as there was no effect of quercetin on sperm lipid peroxidation.     

Patient noncompliance with self-administered chemotherapy

The contribution of patient factors to nonadherence with self-administered cancer chemotherapy along with its prevalence was studied. Fifty-one patients with breast cancer enrolled in protocols that included the orally administered medications Cytoxan (cyclophosphamide) and/or prednisone were interviewed and assessed at five points in time over a 6-month period. Two summary measures of patient nonadherence derived by self-report were developed: (1) dosage, the overall percentage of drug missed during 26 weeks of treatment; and (2) behavioral, the percentage of behavioral events or prescribing occasions on which a criterion level of drug was missed. Twenty-two patients (43%) met criteria for noncompliance according to both behavioral and dosage definitions. Univariate analyses showed more nonadherence in the clinic and private community settings than in the academic setting. Stepwise multiple logistic regression analyses assessed the contribution of patient demographic, psychologic, and physical symptom factors on patient noncompliance. In the regression analyses patient noncompliance was associated with (1) treatment location, more nonadherence in the private community-based treatment sector than in the academic setting; and (2) income, more nonadherence among those having lower incomes. In assessing total dose requirements in clinical research trials, rates of patient nonadherence need to be considered, and treatment location controlled.     

Immune phenotype of peripheral blood mononuclear cells in patients with high-risk non-muscle invasive bladder cancer

Purpose

To explore the immune phenotype of peripheral blood mononuclear cells (PBMC) in patients with high-risk non-muscle invasive bladder cancer (NMIBC).

Methods

We prospectively collected blood samples from patients with high-risk NMIBC treated at our institution. PBMC were analyzed by flow cytometry to determine the frequency of T cells and NK cells and the expression of immunoregulatory molecules (Tim-3, TIGIT and PD-1). PBMC from healthy donors (HD) were included for comparison, and associations with response to BCG were investigated.

Results

A total of 38 patients were included, 19 BCG responders and 19 BCG refractory. Compared to 16 PBMC from HD, the frequency of total NK cells was significantly higher in patients with NMIBC [15.2% (IQR: 11.4, 22.2) vs. 5.72% (IQR: 4.84, 9.79); p?=?0.05], whereas the frequency of T cells was not statistically different. Both Tim-3 and TIGIT expressions were significantly higher in NMIBC compared to HD, particularly in NK cells [13.8% (11.0; 22.4) vs. 5.56% (4.20; 10.2) and 34.9% (18.9; 53.5) vs. 1.82% (0.63; 5.16), respectively; p?<?0.001]. Overall, the expression of PD-1 in all cell types was low in both NMIBC patients and HD. The immune phenotype was not significantly different before and after initiation of BCG. However, the proportion of CD8⁺ T cells before BCG was significantly higher in responders.

Conclusion

The immune phenotype of PBMC from patients with high-risk NMIBC was significantly different from HD, regardless of the presence of disease or the initiation of BCG. Peripheral CD8⁺ T cells could play a role in response to BCG.

     

Physical and functional correlations of ankle-foot orthosis use in the rehabilitation of stroke patients

OBJECTIVE: To examine factors associated with the use of ankle-foot orthoses (AFOs) in stroke patients undergoing rehabilitation. DESIGN: Retrospective cohort study of the frequency of AFO use. SETTING: Inpatient rehabilitation unit. PARTICIPANTS: Consecutive stroke patients (n = 423) admitted to an inpatient rehabilitation unit over a 10-year period. INTERVENTION: Discharge with AFO. MAIN OUTCOME MEASURES: Functional outcome measurement scores of patients who were and who were not prescribed an AFO were examined. The groups were compared by using admission and discharge Chedoke-McMaster Stroke Impairment Inventory (CM; each measure analyzed separately), FIMtrade mark instrument (walking, stairs, overall measures), and Berg Balance Scale scores. RESULTS: Ninety-three of the 423 patients (22%) were discharged with an AFO. Overall, they scored consistently lower than patients who were discharged without an AFO. Statistically significant differences (p <.001) were noted between AFO users and nonusers in admission and discharge scores in the arm, hand, leg, and foot components of the CM and the FIM stairs and walking component scores. Average admission and discharge Berg scores differed between the 2 groups (p =.005, p =.013, respectively). Overall FIM scores were also significantly different both at admission and discharge (p <.001, p =.025, respectively). CONCLUSION: Use of AFOs at discharge was associated with significantly lower admission and discharge CM scores of the arm, hand, leg, and foot; FIM walking and stairs scores; total FIM scores; and Berg Balance Scale scores.