Decreased accumulation of endogenous brain-derived neurotrophic factor against constricting sciatic nerve ligatures in streptozotocin-diabetic and galactose-fed rats

Anterograde and retrograde trafficking of brain-derived neurotrophic factor (BDNF) was examined in streptozotocin-diabetic and galactose-fed rats by measuring accumulation of endogenous neurotrophin proximal and distal to two constricting sciatic nerve ligatures and by direct injection of radiolabeled neurotrophin into the sciatic nerve. Compared to controls, accumulation of endogenous BDNF proximal and distal to the ligatures as well as basal levels in non-ligated nerve segments were decreased in streptozotocin-diabetic and galactose-fed rats. Neither streptozotocin diabetes nor galactose intoxication affected the amount of 125I-labeled BDNF retrogradely transported to the DRG after injection into the sciatic nerve. These results suggest that reduced anterograde and retrograde accumulations of BDNF in experimental diabetes are not a result of impaired capacity for receptor-mediated transport.     

Public, animal, and environmental health implications of aquaculture.

Aquaculture is important to the United States and the world''s fishery system. Both import and export markets for aquaculture products will expand and increase as research begins to remove physiologic and other animal husbandry barriers. Overfishing of wild stock will necessitate supplementation and replenishment through aquaculture. The aquaculture industry must have a better understanding of the impact of the "shrouded" public and animal health issues: technology ignorance, abuse, and neglect. Cross-pollination and cross-training of public health and aquaculture personnel in the effect of public health, animal health, and environmental health on aquaculture are also needed. Future aquaculture development programs require an integrated Gestalt public health approach to ensure that aquaculture does not cause unacceptable risks to public or environmental health and negate the potential economic and nutritional benefits of aquaculture.     

The Bateman function revisited: A critical reevaluation of the quantitative expressions to characterize concentrations in the one compartment body model as a function of time with first-order invasion and first-order elimination

The Bateman function, $A''(e^{ - k_e t} - e^{ - k_a t} )$ , quantifies the time course of a first-order invasion (rate constant k_a) to, and a first-order elimination (rate constant k_e) from, a one-compartment body model where A″=(γDose)k_a/(k _a?k _e) V. The rate constants (whenk _a>3k _e) are frequently determined mined by the “method of residuals” or “feathering”. The rate constantk _a is actually the sum of rate constants for the removal of drug from the invading compartment. “Flip-flop”, the interchange of the values of the evaluated rate constants, occurs whenk _e>3k _a. Whether ?k _a or ?k _e is estimable from the terminal lnC-t slope can be determined from which apparent volume of distribution,V, derived from the Baterman function is the most reasonable. The Bateman function and “feathering” fail when the rate constants are equal. The time course is then expressed byC=γDtk e ^?kt . The determination of such equalk values can be obtained by the nonlinear fitting of suchC-t data with random error to the Bateman function. Also, rate constant equality can be concluded when 1/t _max and the k _min (value ofk _e at the minimum value of $e^{ - k_e t_{max} } /k_e$ plotted against variablek _e values) are synonymous or whenk _min t _max approximates unity. Simpler methods exist to evaluateC-t data. When a drug has 100% bioavailability, regression ofDose/V/C onAUC/C in the nonabsorption phase givesk _e no matter what is the ratio ofm=k _a /k _e . Sincek _e t _max=lnm/(m?1),m can be determined from the given table relatingm andk _e t _max. When γ is unknown,k _e can be estimated from the abscissas of intersections of plots of $C_{max} e^{k_e t_{max} }$ andk _e AUC, both plotted vs. arbitrary values ofk _e, and γD/V values are estimable from the ordinate of the intersection. Also, when γ is unknown,k _e can be estimated from the abscissas of intersections (or of closest approaches) of $e^{k_e t_{max} } /k_e$ andAUC/C _max, both plotted vs. arbitrary values ofk _e. TheC-t plot of the Modified Bateman function, $C = Be^{ - \lambda _2 t} - Ae^{ - \lambda _1 t}$ , does not commence at the origin (i.e., whent _c=0=0 and when a lag time does not exist). However,T _C=0 = ln(A/B/(λ₁-λ₂ whenA>B. AUC ^A″ without time lag is the same asAUC ^A≠B and $A'' = Be^{ - \lambda _2 t} = Ae^{ - \lambda _1 t}$ . Thet _max of theC-t plot of the latter ist _c=0 later than thet _max of theC-t plot of the former which commences att=0. However, (AUMC _uncorr ^A≠B )_∞ =B/λ ₂ ² -A/λ ₁ ² differs fromAUMC _corr ^A≠B ) =A″t _C=0 (1/λ₂-1/λ₁ +A″(1/λ ₂ ² -1/λ ₁ ² ). (AUMC _corr ^A″ ) =A″(1/λ ₂ ² -1/λ ₁ ² ) whenC-t plots start att=0.AUMC _uncorr ^{A ≠ B} is not valid. The (MRT _uncorr ^{A ≠ B} )_∞ is also an invalidMRT estimate, $(B/\lambda _2^2 - A/\lambda _1^2 )/e^{t_{c = 0} } (B/\lambda _2 - A/\lambda _1 )$ , but whenA>B, C-t curves which start at the origin,C _t=0 , haveMRT values displaced byMRT _corr ^{A ≠ B} =MRT ^{[A′ or A' = A = B]} ; +t _C=0 . Thet _max of the Bateman function is also displaced byt _C=0 when theA exceeds theB of its modified form. Dose-dependent pharmacokinetics can be concluded fromC-t data generated by various firstorder invading nonintravenous doses if drug absorption is 100%. Thek _e values can be determined if the apparent volume of distribution of the one-compartment body model is known. Plots ofm/AUC _t ^p vs. timet have a slope of — CL_ME, (the negative of the clearance of the metabolite) and an intercept of the clearance of the precursor, CL_PM, provided that all of the precursor had been absorbed. Similar studies could determine the appararent volume of distribution of the metabolite and the clearance (and thus the rate constant,k _PM=CL_PM/V _P) of the precursor to the metabolite.     

The effects of dopamine agonists on rotational behavior in non-tolerant and caffeine-tolerant rats

Tolerance develops to caffeine-induced stimulation of both locomotor activity and rotational behavior. The role of dopamine in tolerance to the locomotor stimulant effects of caffeine has been documented. However, the role of dopamine in caffeine-induced turning behavior remains to be elucidated. Therefore, the present study determined the role of dopamine receptors in tolerance to caffeine-induced rotational behavior. Rats with a unilateral lesion of the nigrostriatal tract, induced by 6-hydroxydopamine (6-OHDA), were treated chronically with either caffeine (1.0mg/ml) or with drug-free tap water, by a method of scheduled access. Agonists with and without selectivity for dopamine receptor sub-types were tested in both groups of rats (nonselective: apomorphine, d-amphetamine; D1 selective: SKF-38393, SKF-77434; D2 selective: R(-)-propylnorapomorphine (NPA), quinpirole). All drugs produced dose-dependent increases in turning that, with the exception of quinpirole, were comparable in both groups. Quinpirole produced a smaller effect in rats treated with caffeine than in control rats. Thus, there was significant cross-tolerance only to the effects of quinpirole. The concurrent administration of SKF-38393 with NPA produced a synergistic interaction on rotational behavior in control rats, to which cross-tolerance did not develop in caffeine-treated rats. In contrast to what occurs with locomotor activity, in control rats the selective D1 dopamine receptor antagonist SCH 23390 completely blocked SKF-38393-induced turning behavior and the selective D2 dopamine receptor antagonist eticlopride partially attenuated this effect. NPA-induced turning behavior was blocked only by eticlopride; SCH 23390 was without effect. Both SCH 23390 and eticlopride blocked d-amphetamine-induced rotational behavior. The results of this study suggest that D1 dopamine receptors are not involved in tolerance to caffeine-induced rotational behavior. The role of D2 dopamine receptors in this effect is unresolved. Results obtained from rotational behavior studies generally do not parallel those obtained from locomotor activity studies, suggesting that different mechanisms underlie the effects of caffeine on these two behaviors.     

Cannabis use and cognitive decline in persons under 65 years of age

The purpose of this study was to investigate possible adverse effects of cannabis use on cognitive decline after 12 years in persons under age 65 years. This was a follow-up study of a probability sample of the adult household residents of East Baltimore. The analyses included 1,318 participants in the Baltimore, Maryland, portion of the Epidemiologic Catchment Area study who completed the Mini-Mental State Examination (MMSE) during three study waves in 1981, 1982, and 1993-1996. Individual MMSE score differences between waves 2 and 3 were calculated for each study participant. After 12 years, study participants' scores declined a mean of 1.20 points on the MMSE (standard deviation 1.90), with 66% having scores that declined by at least one point. Significant numbers of scores declined by three points or more (15% of participants in the 18-29 age group). There were no significant differences in cognitive decline between heavy users, light users, and nonusers of cannabis. There were also no male-female differences in cognitive decline in relation to cannabis use. The authors conclude that over long time periods, in persons under age 65 years, cognitive decline occurs in all age groups. This decline is closely associated with aging and educational level but does not appear to be associated with cannabis use.     

Commentary and historical perspective of anterior cruciate ligament rehabilitation

This article serves as the introduction and historical perspective of anterior cruciate ligament surgery and rehabilitation. Several physician-therapist teams have been invited to share their "state of the art" techniques and to contrast their programs to that espoused by Shelbourne and Nitz in 1990. Our commentary/review of "Accelerated Rehabilitation After Anterior Cruciate Ligament Reconstruction" (Shelbourne KD, Nitz P, Am J Sports Med 18:292-299, 1990) is provided to contextualize the reader to what most clinicians would recognize as an extremely aggressive rehabilitation approach that is being popularized in the 1990s. A comparison is then presented of the rehabilitation sequence used in the MacIntosh procedures, demonstrating how early motion/functional rehabilitation was the hallmark of this type of extraarticular rehabilitation sequence and how today's pattern has evolved to follow that philosophy. Each of the teamed authors has attempted to present his surgery and rehabilitation/techniques and highlight differences between his program and that of Shelbourne and Nitz. We hope that the readers find this glimpse of the past and present helpful in formulating their rehabilitation sequences and that the future will be predicated on excellent basic science and clinical judgment. J Orthop Sports Phys Ther 1992;15(6):265-269.     

Abdominal musculature abnormalities as a cause of groin pain in athletes. Inguinal hernias and pubalgia.

There has been increasing interest within the European sports medicine community regarding the etiology and treatment of groin pain in the athlete. Groin pain is most commonly caused by musculotendinous strains of the adductors and other muscles crossing the hip joint, but may also be related to abdominal wall abnormalities. Cases may be termed "pubalgia" if physical examination does not reveal inguinal hernia and there is an absence of other etiology for groin pain. We present nine cases of patients who underwent herniorrhaphies for groin pain. Two patients had groin pain without evidence of a hernia preoperatively (pubalgia). In the remaining seven patients we determined the presence of a hernia by physical examination. At operation, eight patients were found to have inguinal hernias. One patient had no hernia but had partial avulsion of the internal oblique fibers from their insertion at the public tubercle. The average interval from operation to return to full activity was 11 weeks. All patients returned to full activity within 3 months of surgery. One patient had persistent symptoms of mild incisional tenderness, but otherwise there were no recurrences, complications, or persistence of symptoms. Abnormalities of the abdominal wall, including inguinal hernias and microscopic tears or avulsions of the internal oblique muscle, can be an overlooked source of groin pain in the athlete. Operative treatment of this condition with herniorrhaphy can return the athlete to his sport within 3 months.