A Comparative Study of Hummingbirds and Chickens Provides Mechanistic Insight on the Histidine Containing Dipeptide Role in Skeletal Muscle Metabolism.

Histidine containing dipeptides (HCDs) have numerous ergogenic and therapeutic properties, but their primary role in skeletal muscle remains unclear. Potential functions include pH regulation, protection against reactive oxygen/nitrogen species, or Ca2+ regulation. In recognition of the challenge of isolating physiological processes in-vivo, we employed a comparative physiology approach to investigate the primary mechanism of HCD action in skeletal muscle. We selected two avian species (i.e., hummingbirds and chickens), who represented the extremes of the physiological processes in which HCDs are likely to function. Our findings indicate that HCDs are non-essential to the development of highly oxidative and contractile muscle, given their very low content in hummingbird skeletal tissue. In contrast, their abundance in the glycolytic chicken muscle, indicate that they are important in anaerobic bioenergetics as pH regulators. This evidence provides new insights on the HCD role in skeletal muscle, which could inform widespread interventions, from health to elite performance.

Exercise training, creatine supplementation, and bone health in ovariectomized rats.

UNLABELLED: Evidence suggests that creatine may have some beneficial effects on bone. The study aimed to investigate the effects of exercise alone or combined with creatine on bone health in ovariectomized rats. Findings show that exercise, but not creatine, has an important role in improving bone health. INTRODUCTION: The aim of this study was to investigate the effects of exercise training alone or combined with creatine supplementation on bone health parameters in ovariectomized rats. METHODS: Wistar rats were randomly allocated into one of five groups: (i) sham-operated, (ii) ovariectomized non-trained placebo-supplemented, (iii) ovariectomized non-trained creatine-supplemented, (iv) ovariectomized exercise-trained placebo-supplemented, and (v) ovariectomized exercise-trained creatine-supplemented. Downhill running training and/or creatine supplementation (300 mg/kg body weight) were administered for 12 weeks. Bone mineral content (BMC), bone mineral density (BMD), and biomechanical and histomorphometric parameters were assessed. RESULTS: No interaction effects were observed for BMC and BMD at whole body, femur, and lumbar spine (p > 0.05). Importantly, a main effect of training was detected for whole body BMC and BMD (p = 0.003 and p < 0.001, respectively), femoral BMC and BMD (p = 0.005 and p < 0.001, respectively), and lumbar spine BMC and BMD (p < 0.001 and p < 0.001, respectively), suggesting that the trained animals had higher bone mass, irrespective of creatine supplementation. Main effects of training were also observed for maximal load (p < 0.001), stiffness (p < 0.001), and toughness (p = 0.046), indicating beneficial effects of exercise training on bone strength. Neither a main effect of supplementation nor an interaction effect was detected for biomechanical parameters (p > 0.05). No main or interaction effects were observed for any of the histomorphometric parameters evaluated (p > 0.05). CONCLUSIONS: Exercise training, but not creatine supplementation, attenuated ovariectomy-induced bone loss in this rat model.

Circadian rhythm of melatonin and prostaglandin in modulation of stress-induced gastric mucosal lesions in rats.

BACKGROUND: We previously demonstrated the circadian variation of water-immersion restraint stress (WRS)-induced gastric mucosal lesions in rats. AIM: To investigate the roles of melatonin and prostaglandin in the gastric mucosa in circadian modulation of WRS. METHODS: Fasted rats were subjected to 4-h WRS during both the diurnal and nocturnal phases of a light/dark cycle. Mucosal lesions, serum melatonin concentrations, mucosal generation of prostaglandin E2 (PGE2) and mucosal gene expressions of cyclooxygenase (COX)-1 and -2 were evaluated. RESULTS: Lesion area after 4-h stress during the dark phase was significantly smaller than that in light-phase controls. Serum melatonin concentration in control rats during the light phase was significantly increased 4 h after WRS, but PGE2 generation was decreased by 48% as compared to that in intact mucosa before stress. In the dark phase, melatonin concentration after 4-h WRS was significantly depressed as compared with the control level at the corresponding time. PGE2 concentrations after 4-h WRS in the dark phase were not decreased compared with the control level at the corresponding time, although PGE2 level was significantly lower than that in light-phase controls. Expression of COX-1 and COX-2 mRNA was detected after exposure to stress in both the light and dark phases. CONCLUSION: These results suggest that circadian rhythm has an important role in the formation of stress-induced gastric mucosal lesions in rats. The circadian rhythm of melatonin responses and PGE2 generation may contribute to nocturnal/diurnal rhythmicity of gastric mucosal defences between day and night.

Pathologic mechanism of experimental scoliosis in pinealectomized chickens.

STUDY DESIGN: This study was designed to investigate the pathologic mechanisms of idiopathic scoliosis using experimentally induced scoliosis in chickens. OBJECTIVE: To understand the process of producing a scoliotic deformity in pinealectomized chickens. SUMMARY OF BACKGROUND DATA: Pinealectomy in chickens consistently produces scoliosis with anatomic characteristics similar to those of human idiopathic scoliosis. Pinealectomized chickens are an important animal model for the study of idiopathic scoliosis. METHODS: In this study, 40 chickens were divided into two groups; 20 chickens treated with pinealectomy and 20 with a sham operation as control subjects on the second after hatching. The chickens in both groups then were killed at intervals ranging from 1 to 20 weeks after surgery. Their spines were examined visually and radiologically for the presence of a scoliotic curve and vertebral deformities. RESULTS: Rotational lordoscoliosis developed in pinealectomized chickens. The chickens with severe scoliosis were characterized by apically wedge-shaped vertebrae. In contrast, no scoliosis with any vertebral deformity developed in any of the chickens that received a sham operation. CONCLUSIONS: Because there normally is evidence of lordosis in the thoracic spine of chickens, the rotational instability of the spine induced by pinealectomy may produce a scoliotic deformity as a secondary phenomenon. Pinealectomy in chickens consistently produces scoliosis with anatomic characteristics similar to those of human idiopathic scoliosis. The authors believe that disturbance of the equilibrium and the posture mechanism associated with a defect in melatonin synthesis after pinealectomy may promote the development of rotational lordoscoliosis.

Roles of nocturnal melatonin and the pineal gland in modulation of water-immersion restraint stress-induced gastric mucosal lesions in rats.

The roles of melatonin and the pineal gland in the circadian variation of water-immersion restraint stress-induced gastric mucosal lesions in rats were investigated. Fasted rats were subjected to water-immersion restraint stress during both the diurnal and nocturnal phases of a light:dark cycle. Pinealectomized and sham-operated rats were also subjected to water-immersion restraint stress at night. The lesion area after 4 hr of stress during the dark phase was significantly lower than in light-phase controls. Pinealectomy increased the lesion area in the dark phase, compared to the sham operation, but this effect was counteracted by intracisternal melatonin preadministration at a dose of 100 ng/rat. Melatonin concentrations in control rats during the light phase were significantly increased 4 hr after water-immersion restraint stress. In contrast, melatonin concentrations 4 hr after water-immersion restraint stress in the dark phase were significantly depressed compared with the control levels at the corresponding time. Melatonin levels after stress exposure were markedly decreased in pinealectomized rats as compared with sham-operated rats. These results suggest that circadian rhythm has an important role in the formation of stress-induced gastric mucosal lesions in rats and that melatonin responses to water-immersion restraint stress differ between day and night. The pineal gland modulates the stress response and melatonin contributes to gastric protection via a mechanism involving the central nervous system.

Melatonin's gastroprotective and antistress roles involve both central and peripheral effects.

Systemic administration of melatonin (5 to 20 mg/kg) has been reported to inhibit the induction of acute gastric mucosal lesions by stress or ischemia-reperfusion in rats. We recently demonstrated that intracisternal (i.c.) melatonin at low doses (1 to 100 ng) dose-dependently decreased acid and pepsin outputs in rats. The aim of the present study was to further investigate the peripheral and central roles of melatonin in gastric mucosal defense. Using a radioimmunoassay, we measured melatonin concentrations in the plasma and cerebrospinal fluid (CSF) of the cisterna magna in rats subjected to water immersion restraint stress and given intraperitoneal (i.p.) or i.c. injection of melatonin. Water immersion restraint stress was followed by a significant duration-related increase in peripheral plasma melatonin levels; the stress similarly produced a time-dependent increase in the extent of gastric mucosal lesions. Administration of melatonin (1 or 10 mg/kg, i.p., or 100 ng/10 microl, i.c.) significantly reduced the extent of stress-induced gastric damage, by 46%, 67%, and 54%, respectively. The effective i.c. dose of melatonin was at least 10,000-fold smaller than the effective i.p. dose. Melatonin levels in plasma and CSF after the i.p. injection of melatonin at 10 mg/kg were dramatically higher than those after the i.c. injection of vehicle or 100 ng of melatonin. Our results suggest that the peripheral gastroprotective action of melatonin should be investigated with due regard to these central effects.

The pineal gland is not essential for circadian expression of rat period homologue (rper2) mRNA in the suprachiasmatic nucleus and peripheral tissues.

To investigate the functional involvement of the pineal gland in circadian expression of the rat period homolog gene (rPer2) in the suprachiasmatic nucleus (SCN) and peripheral tissues, we performed Northern blot analysis in tissues from pinealectomized rats. The ectomy did not have any significant effects on rPer2 mRNA expression patterns both in a daily light-dark condition and in a constant darkness. These results suggest that the rhythmic secretion of pineal melatonin is not essential for the circadian expression of clock genes in the SCN and other peripheral tissues of rats.

Pathogenesis of idiopathic scoliosis. Experimental study in rats.

STUDY DESIGN: A radiographic examination of pinealectomized rats to observe the development of scoliosis and halt the condition by administration of melatonin. OBJECTIVES: To discover whether pinealectomy has the same effect in mammals as shown in the chicken, and to determine whether the bipedal condition is important for development of scoliosis. SUMMARY OF BACKGROUND DATA: Pinealectomizing chickens shortly after hatching consistently resulted in scoliosis closely resembling human idiopathic scoliosis. It has not been determined whether this phenomenon is restricted solely to chickens, or if this experimental model is applicable to other animals, especially those more closely related to humans. METHODS: A sham operation in five bipedal rats served as the control in this study. Pinealectomy was performed in 10 quadrupedal rats, pinealectomy in 20 bipedal rats, and pinealectomy with implantation of melatonin pellet in 10 bipedal rats. Spinal radiographs were used to measure the degree of scoliosis at 3 months after surgery. RESULTS: Scoliosis developed only in pinealectomized bipedal rats and not in quadrupedal rats. It developed in none of the sham operation group and in only 1 of 10 pinealectomized bipedal rats with melatonin treatment. CONCLUSIONS: Melatonin deficiency secondary to pinealectomy alone does not produce scoliosis if the quadrupedal condition is maintained. The bipedal condition, such as that in chickens or humans, plays an important role in the development of scoliosis. The findings suggest a critical influence of a postural mechanism for the development of scoliosis.

Central nervous system action of melatonin on gastric acid and pepsin secretion in pylorus-ligated rats.

We recently demonstrated that centrally administered melatonin at low doses inhibits the induction of gastric lesions by water-immersion restraint stress. To investigate the mechanism of the potent anti-ulcer action of melatonin, the central nervous system (CNS) effects of melatonin on gastric acid and pepsin secretion were studied in conscious pylorus-ligated rats. Intracisternal (i.c.) melatonin (1-100 ng) dose-dependently decreased acid and pepsin output, while a higher i.p. dose (1 microg) had no inhibitory effect. The i.c. melatonin did not change serum gastrin concentrations. Serum melatonin concentrations at 1 and 4 h after i.c. administration of 10-100 ng melatonin did not differ from those in rats receiving i.c. vehicle. The present results suggest that melatonin administered centrally modulates the secretion of gastric acid and pepsin which may explain, at least in part, the protective, anti-stress role of melatonin in the gastric mucosa observed in our previous study.

Alteration by maternal pinealectomy of fetal and neonatal melatonin and dopamine D1 receptor binding in the suprachiasmatic nuclei.

The effects of maternal melatonin on fetal and neonatal melatonin and dopamine D1 receptor systems in the central nervous system, mainly in the suprachiasmatic nuclei (SCN), were investigated after pinealectomy of rats at day 7 of pregnancy. 125I-labelled iodomelatonin injected intravenously into the pregnant rats (at day 21) was transferred in considerable amount into the fetal circulation. In vitro autoradiography data demonstrated an increase in the melatonin binding activity in the fetal (embryonic day 21) and early postnatal SCN (postnatal day 3) caused by maternal pinealectomy. This upregulation of the melatonin receptor in the SCN was then normalized after the melatonin system of the neonate started to work. The pregnant rats themselves did not show such a change in their melatonin receptors in the SCN following pinealectomy. Dopamine D1 receptor binding was affected by pinealectomy exclusively in the SCN of fetal and neonatal rats as well as in that of mothers. These results clearly indicate that the fetal circadian clock in the SCN is controlled and prepared before birth to some extent by maternal melatonin rhythm.

Central nervous system action of melatonin on gastric acid and pepsin secretion in pylorus-ligated rats.

We recently demonstrated that centrally administered melatonin at low doses inhibits the induction of gastric lesions by water-immersion restraint stress. To investigate the mechanism of the potent anti-ulcer action of melatonin, the central nervous system (CNS) effects of melatonin on gastric acid and pepsin secretion were studied in conscious pylorus-ligated rats. Intracisternal (i.c.) melatonin (1-100 ng) dose-dependently decreased acid and pepsin output, while a higher i.p. dose (1 microg) had no inhibitory effect. The i.c. melatonin did not change serum gastrin concentrations. Serum melatonin concentrations at 1 and 4 h after i.c. administration of 10-100 ng melatonin did not differ from those in rats receiving i.c. vehicle. The present results suggest that melatonin administered centrally modulates the secretion of gastric acid and pepsin which may explain, at least in part, the protective, anti-stress role of melatonin in the gastric mucosa observed in our previous study.

Protective role of melatonin and the pineal gland in modulating water immersion restraint stress ulcer in rats.

We investigated the protective effect of melatonin on stress-induced gastric lesions in rats. Fasted rats were subjected to water immersion restraint stress for 4 h and the percentage of corpus mucosa containing hemorrhagic lesions was determined. Thirty minutes before restraint stress, melatonin or vehicle was administered i.p. In another experiment, pinealectomy was performed 1 week before water immersion restraint stress. Administration of melatonin at 1 and 5 mg/kg significantly decreased gastric lesions by 46 and 74%, respectively. In contrast, pinealectomy significantly enlarged the lesion area, although this effect was counteracted by melatonin at a dose of 1 mg/kg i.p. However, this protective effect of melatonin was abolished by i.p. pretreatment with indomethacin at 5 mg/kg. These results suggest that melatonin has gastroprotective properties against stress-induced gastric injury in rats and that the pineal gland contributes to gastric protection via prostaglandin-dependent mechanisms.

Central effect of melatonin against stress-induced gastric ulcers in rats.

We investigated the role of melatonin in the induction of gastric lesions induced by water immersion restraint stress or centrally administered thyrotropin-releasing hormone (TRH). Melatonin (0.1-1 ng) injected intracisternally (i.c) 30 min prior to stress dose-dependently inhibited the induction of gastric lesions by water immersion restraint stress, while 100 micrograms/kg, i.p. failed to protect the gastric mucosa. Preadministration of melatonin (1 ng, i.c.) significantly reduced (83%) the severity of gastric lesions induced by a TRH analogue (500 ng, i.c.). Serum melatonin concentrations 30 min after administration of 1 ng melatonin i.c. did not differ from those of rats receiving i.c. vehicle. These results suggest that melatonin plays a protective, anti-stress, role in the gastric mucosa via a mechanism involving the central nervous system.

Role of serotonin for scoliotic deformity in pinealectomized chicken.

STUDY DESIGN: The effect of intraperitoneal injection of 5-hydroxytryptophan (5-HTP) versus control in pinealectomized chickens. OBJECTIVE: To find if the serotonin may have some role in the cause of treatment of idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: One of the causes of idiopathic scoliosis is thought to be the disruption of postural reflex. Serotonin has been proposed to have a crucial role in maintaining normal postural muscle tone or postural equilibrium. METHOD: Forty pinealectomized chickens served as controls, and an additional 40 pinealectomized chickens received daily intraperitoneal injections of 5-hydroxy-tryptophan, a precursor of serotonin, which can pass through the blood-brain barrier. Spine radiographs were examined to measure the scoliotic deformity. RESULTS: Scoliosis developed in all 40 pinealectomized chickens (control), whereas only 28 chickens in the 5-hydroxytryptophan-treated group (6 in severe, 22 in mild) had scoliosis developed. The remaining 12 chickens grew up with normal spines. Most chickens with mild scoliosis did not have curve progression but continued to have wedged vertebrae. CONCLUSION: Serotonin deficit secondary to a defect of melatonin may have disturbed postural muscle tone or postural equilibrium resulting in scoliosis in pinealectomized chicken. Prevention from the development of scoliosis or its progression in chickens treated with 5-hydroxytryptophan suggests that serotonin may have potential therapeutic value.

Changes in the E/A ratio induced by handgrip-exercise are related to changes in the plasma atrial natriuretic peptide level, but not to changes in brain natriuretic peptide in mild essential hypertension.

We investigated the relationship between changes in atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and changes in cardiac function during mild exercise in patients with mild hypertension. The handgrip test (HGT) was performed by 21 untreated, mildly hypertensive patients, mean age 45 +/- 5 years. M-mode and pulse Doppler echocardiograms were recorded before and during HGT. In 7 patients (Group A), diastolic function, which was determined by the peak early velocity and peak atrial velocity (E/A) ratio using Doppler echocardiography was attenuated during HGT (1.19 +/- 0.21 TO 1.04 +/- 0.16, p < 0.05). There was no change in diastolic function in the remaining 14 patients, left atrial diameter, cardiac index, ejection fraction, plasma renin activity, plasma norepinephrine, blood pressure, nor heart rate were different between the two groups. While ANP was increased in Group A during HGT (from 41.0 +/- 18.2 to 54.0 +/- 24.1 pg/ml, p < 0.05) it was unchanged in Group B (36.8 +/- 16.3 to 33.5 +/- 11.9 pg/ml). BNP did not change in either Group (Group A: 2.9 +/- 3.1 to 3.0 +/- 3.4 pg/ml, Group B: 2.6 +/- 1.6 to 3.6 +/- 4.8 pg/ml). The percent change in ANP during HGT did not correlate with the percent change in BNP. Thus, the impairment of cardiac functional reserve appeared to influence ANP excretion in patients with mild hypertension.

[A case of encephalopathy accompanying Mycoplasma pneumoniae pneumonia in an adult].

We experienced a 39-year-old male who developed neurological complication during a course of Mycoplasma pneumoniae pneumonia. The diagnosis of M. pneumoniae pneumonia was made on the basis of elevation of specific antibody (CF) titer in convalescent serum. Electroencephalogram showed diffuse damage in the brain, but no other abnormalities were not found on brain CT-scan and MRI. In the cerebrospinal fluid, the number of cells did not increase and the M. pneumoniae CF titer was not elevated. From these results, we concluded that encephalopathy in this patient was raised by an allergic reaction of the brain tissue to M. pneumoniae antigen. Until now, encephalitis or meningoencephalitis accompanied with M. pneumoniae infection has been reported by many investigators, but reports on encephalopathy due to M. pneumoniae are few. Therefore, we reported herein a case of encephalopathy following Mycoplasma pneumoniae pneumonia with several references.

Effects of intracerebroventricular injection of indomethacin on adaptive gastric cytoprotection in the conscious rat.

We investigated the role of prostaglandins in the central nervous system for the adaptive gastric cytoprotection in male Wistar rats with chronic intracerebroventricular cannulas. Three, 50, 200, or 500 micrograms of indomethacin or vehicle alone was injected via the intracerebroventricular (central) or intraperitoneal route 1 h before oral administration of 20% ethanol. The animals were then given 1 ml of absolute ethanol 15 min later. One hour later, gastric mucosal damage and plasma indomethacin concentrations were measured. Pretreatment with 50-500 micrograms of indomethacin abolished adaptive gastric cytoprotection induced by 20% ethanol in a dose-dependent fashion, regardless of the route of administration. Central administration of 3 micrograms indomethacin resulted in a more than twofold increase in mucosal damage compared with intraperitoneal administration. Plasma indomethacin concentrations were increased dose-dependently. However, plasma levels were lower in rats administered centrally than those peripherally at a dose of 50 micrograms indomethacin or more. On the other hand, plasma indomethacin concentrations did not differ between central and intraperitoneal administration of 3 micrograms indomethacin. Measurement of gastric mucosal blood flow revealed that central administration of 3 micrograms indomethacin reduced gastric mucosal blood flow, whereas intraperitoneal administration of an identical dose had no effect. These results suggest that central prostaglandins may contribute to adaptive gastric cytoprotection, possibly by altered gastric mucosal blood flow.

Role of mucosal prostaglandins in vagally-mediated adaptive cytoprotection in the rat.

This study was designed to investigate whether vagal innervation and mucosal prostaglandins (PGs) participate in gastric adaptive cytoprotection. Rats were divided into three groups; sham operation (control), truncal vagotomy or splanchnicotomy. In the first experiment, 100% ethanol (EtOH) was orally administered 15 min after pretreatment with 20% EtOH to all 3 groups. One hour later, the gastric mucosa was examined macroscopically. In a second experiment, the mucosal PG contents 15 min after administration of either 20% EtOH or saline were measured by high performance liquid chromatography. In truncal vagotomized rats, the adaptive cytoprotection caused by exposure to 20% EtOH in control and splanchnicotomized rats was not observed and an increase in hemorrhagic lesion severity was seen. In the control and splanchnicotomized rats, PGE2 contents were elevated following 20% EtHO treatment, as compared to those in the saline-treated rats. However, PGE2 contents in vagotomized rats were not altered by EtOH exposure, and were significantly lower than in the control and splanchnicotomized groups, whereas PGF2 alpha and PGD2 contents were significantly higher after EtOH administration as compared to those in saline-treated rats. These results suggest that vagal innervation is essential for adaptive cytoprotection and that the vagotomy-induced decrease in PGE2 and increases in PGF2 alpha and PGD2 following 20% EtOH administration, may be caused by a disturbance in adaptive cytoprotection.

Detection of varicella-zoster virus DNA by polymerase chain reaction in cerebrospinal fluid of patients with herpes zoster meningitis.

In three of five patients with herpes zoster meningitis, varicella-zoster virus (VZV) DNA was detected by the polymerase chain reaction (PCR) in the initial samples of cerebrospinal fluid. DNA fragments of group A or B, following classification of VZV strains by the size of the variable region IV of VZV genome, were found at the 7th, 10th and 24th illness day in the three positive cases: one of these cases did not have skin lesions. These results suggest that the detection of VZV DNA by PCR is useful for the diagnosis of herpes zoster meningitis, as well as for its molecular epidemiology.