Relationship between physiological loss, performance decrement, and age in master athletes

BACKGROUND: The use of master athletes to describe an idealized rate of physiological loss associated with aging is quite common. The results of such studies suggest that older athletes may be able to reduce the rate of decline in functional loss. The findings of such studies have been questioned due to their limited sample size and the age range and gender of their subjects. METHODS: We examined a group of 146 male and 82 female master athletes over the age of 40 years. Physiological parameters included maximal oxygen uptake (VO2max), body composition, muscle strength, bone density, and blood chemistries. Medical histories and training records were obtained via questionnaire. RESULTS: Results demonstrated gender differences in body composition, blood chemistries, blood pressure, VO2max, muscle strength, bone density, and performance (p <.05). All metabolic parameters for men and most for women demonstrated significant losses across the age range (p <.05). In addition, strength and performance for men and women and bone density for women declined significantly with age (p <.05). The demonstrated loss rates did not differ by gender. CONCLUSIONS: Although limited by the lack of a sedentary comparison group, these data suggest that age-related losses in VO2max may not be different from data previously reported for older sedentary adults and that loss in muscle strength and performance with aging is not linear.     

Role of GAP-43 in mediating the responsiveness of cerebellar and precerebellar neurons to axotomy

To determine whether the competence for axonal sprouting and/or regeneration in the cerebellar system correlates with GAP-43 expression, we have studied GAP-43 mRNA and protein expression in the postlesioned cerebellum and inferior olive. Purkinje cells transiently express GAP-43 during their developmental phase (from E15 to P5 in the rat) which consists of fast axonal growth and the formation of the corticonuclear projection. Adult Purkinje cells, which in control adult rats do not express GAP-43, are extremely resistant to the effects of axotomy but cannot regenerate axons. However, a late and protracted sprouting of axotomized Purkinje cells occurs spontaneously and correlates with a mild expression of GAP-43 mRNA. In contrast, inferior olivary neurons, despite their high constitutive expression of GAP-43, do not sprout but retract their axons and die after axotomy. Furthermore, mature Purkinje cells in cerebellar explants of transgenic mice that overexpress GAP-43 do not regenerate after axotomy, even in the presence of a permissive substrate (cerebellar embryonic tissue) and, contrary to the case in wild-type mice, they do not survive in the in vitro conditions and undergo massive cell death. These results show that the expression of GAP-43 is not only associated with axonal growth, but also with neuronal death.     

Dipeptide Derivatives of Primaquine as Transmission-Blocking Antimalarials: Effect of Aliphatic Side-Chain Acylation on the Gametocytocidal Activity and on the Formation of Carboxyprimaquine in Rat Liver Homogenates

Purpose. Dipeptide derivatives of primaquine (PQ) with reduced oxidative deamination to the inactive metabolite carboxypnmaquine were synthesized and evaluated as a novel class of transmission-blocking antimalarials. Methods. Antimalarial activity was studied using a model consisting of mefloquine-resistant Plasmodium berghei ANKA 25R/10, Balb C mice, and Anopheles stephensi mosquitoes. Metabolic studies were performed with rat liver homogenates, and the incubates were analyzed by HPLC. Results. All dipeptide derivatives and glycyl-PQ completely inhibited the appearance of oocysts in the midguts of the mosquitoes at 15 mg/ kg, while N-acetylprimaquine was not active at this dose. However, none of the title compounds were able to block oocyst production at 3.75 mg/kg, in contrast with primaquine. Exception for sarc-gly-PQ, all remaining compounds prevented sporozoite formation in the salivary glands of mosquitoes at a dose of 3.75 mg/kg. Simultaneous hydrolysis to primaquine and gly-PQ ocurred with the following order of V_max/ K_m: for primaquine formation, L-ala-gly-PQ > L-phe-gly-PQ > gly-gly-PQ; and for gly-PQ formation, L-phe-gly-PQ > L-ala-gly-PQ > gly-gly-PQ. In contrast, primaquine was not released from D-phe-gly-PQ, sarc-gly-PQ, and N-acetylprimaquine. Neither carboxyprimaquine nor 8-amino- 6-methoxy- quinoline were detected in any of the incubation mixtures. Conclusions. The title compounds prevent the development of the sporogonic cycle of Plasmodium berghei. Gametocytocidal activity is independent of the rate and pathway of primaquine formation. Acylation of the aliphatic side-chain effectively prevents the formation of Carboxyprimaquine, but the presence of a terminal amino group appears to be essential for the gametocytocidal activity.     

Angiogenesis and expression of estrogen and progesterone receptors as predictive factors for recurrence of meningioma

Meningiomas are benign tumors, with low rate of recurrence after surgery. The most important factor predicting recurrence is the extent of surgical resection; other factors have been studied with conflicting results. Angiogenesis, an important substratum for growth and spread of neoplasic cells, and the expression of estrogen and progesterone receptors (ER, PR), could play a role in the recurrence of meningioma. We evaluated 42 patients with meningioma diagnosis (confirmed by histopathology) treated exclusively by surgery between January 1995 and December 1999, and compared the recurring and non-recurring groups after a ten-year follow-up period. Recurrence was associated with several factors including vascular density (VD), cell proliferation index (CPI), ER, PR, and cyclin E (CE) tissue expression, as evaluated by immunohistochemistry. Complete surgical resection was achieved in 41% of patients. Recurrence of meningioma was found in 17 patients (40%). Median ± standard deviation (SD) of recurrence time was 32 ± 5 months. When recurrence versus no recurrence was compared, mean ± SD of VD and CPI were 9 ± 3.6 and 607.6 ± 233 (40×/10 fields) respectively. Tissue expression was positive for ER, PR, and CE in 28, 62 and 91% of patients, respectively. The sole significant recurrence-associated factors were extent of resection (P = 0.003) and VD (P = 0.004). ER, PR, and CE-tissue expression were not statistically significant. The most important factor associated with meningioma relapse was vascular density, independently of hormonal status and extent of surgical resection. Patients with a high risk of recurrence could benefit from additional treatment.     

Low serum levels of nerve growth factor in diabetic neuropathy

Several structural and functional similarities between nerve growth factor and insulin have been described. Diabetes mellitus, a disease with absolute or relative deficiency of insulin is frequently associated with peripheral neuropathy whose physiopathological mechanisms are obscure. In this study, we measured serum levels of NGF in 18 patients with diabetic neuropathy and 9 healthy controls; patients with diabetic neuropathy had lower levels of NGF than controls (p less than 0.01). When patients were separated in two groups according to degree of impairment of motor nerve conduction velocity, those with more than 10% of impairment, had lower levels of NGF than those with less than 10% of impairment, or controls. It was found a correlation between NGF levels and decrease of motor nerve conduction velocity; then, diabetic neuropathy seems to be associated to low serum levels of NGF, pointing out a possible role of NGF in the pathology of diabetic neuropathy.     

EEG infraslow activity in absence and partial seizures.

It is currently assumed that for recording of infraslow activity (ISA) DC-coupled amplifiers are required. This report will demonstrate that this may not be the case and presents some data about its potential clinical usefulness. Archived EEGs of 29 seizures from 6 children with absence attacks, accompanied by 3 Hz classical spike-wave discharges (SW), were compared with 20 partial seizures from 10 adult patients. The data from the children were acquired on a Bio-logic system, those from the adults on a Grass-Telefactor instrument. In the children the original 30-minute routine EEG was used while in the adults stored videomonitored data were excerpted to provide 20-minute segments which included the preictal, ictal and postictal state. All data were analyzed with the BESA software package. The seizures were evaluated separately on conventional filter settings, full band of 0.01-to the upper limit of the instrument, and 0.01-0.1 Hz (infraslow activity, ISA). Filter settings of 0.01-0.1 Hz provided a better assessment of ISA than when the full band was evaluated. Absence seizures showed bilateral essentially synchronous ISA with a negative positive sequence in the frontal areas and opposite polarity in the posterior head regions. In partial seizures when seizure onset was clearly lateralizeable from conventional frequency settings ISA corresponded to that hemisphere, but the electrode position could be displaced to a neighboring one from the one which was maximally involved on conventional settings. Topographic analysis showed two types of ISA: one with focal spread only and the other where there was in addition an element of synchrony especially in the frontal areas. It is concluded that ISA can be recovered from conventional EEG recordings and may be helpful not only in determining the area(s) of seizure onset but can also differentiate truly focal seizures from those where an additional generalized seizure tendency is present. This is likely to be important when epilepsy surgery is performed in absence of a demonstrable structural lesion.     

Combined use of novel epithelial (MOC-31) and mesothelial (HBME-1) immunohistochemical markers for optimal first line diagnostic distinction between mesothelioma and metastatic carcinoma in pleura

AIMS: To determine the value of immunohistochemistry in differentiation of malignant pleural mesothelioma from carcinoma in a pleural biopsy we optimized a double panel of MOC-31 and HBME-1 and compared the results with others from the literature. METHODS AND RESULTS: A multi-antibody panel was applied to biopsy samples from 44 cases of malignant pleural mesothelioma and 23 cases of carcinoma metastatic to the pleura. We used monoclonal antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen Ber-EP4, carcinoembryonic antigen (CEA), tumour-associated glycoprotein (B72.3), LeuM1, vimentin, desmin, epithelial related antigen (MOC-31) and mesothelial cell (HBME-1). Positivity for MOC-31 and Ber-EP4 was found to have the highest nosologic sensitivity (94.1% and 84.6%, respectively) and specificity (86.3% both antibodies) for carcinoma. Positive staining for HBME-1 and vimentin had the highest sensitivity (90.9% and 100%, respectively) and specificity (91.3% and 60%, respectively) for mesothelioma. A two-marker antibody panel with HBME-1 and MOC-31 was the most efficient for the distinction between carcinoma and malignant pleural mesothelioma. Conclusion: A combination of MOC-31 (an anti- epithelial marker) and HBME-1 (an anti-mesothelial marker) has a diagnostic efficiency of 76.1% for the distinction between carcinoma and mesothelioma in pleura.