Pain and tenderness in human temporal muscle induced by bradykinin and 5-hydroxytryptamine

Pain was induced in 19 healthy individuals by double-blind injections into the temporal muscle of 0.2 ml of physiological saline with or without active substances added. 5-Hydroxytryptamine (2 nmol) caused pain similar to saline, bradykinin (2 nmol) only insignificantly more pain (0.05<p<0.1), while a mixture of the two substances in half dosage (1 nmol + 1 nmol) caused pain significantly above saline (p<0.01). Variations in the response to saline did not permit a conclusion to be made on the question of induced tenderness. However, the mixture of the two substances appeared to lower the pressure-pain threshold as measured by a pressure algometer (p<0.05).     

Ceruletide increases threshold and tolerance to experimentally induced pain in healthy man

Previous studies suggested that ceruletide might be endowed with analgesic and sedative properties. To investigate the effects of ceruletide on experimentally induced pain and on central nervous functions, two studies, each involving 24 healthy subjects, were carried out in random double-blind fashion. Every subject participated in three experiments one week apart. In study 1, 120 and 60 ng/kg/hr ceruletide IV increased threshold and tolerance to electrically and threshold to thermally induced cutaneous pain significantly more than saline (p<0.001), the higher dose being slightly more active. Only mild sedative effects occurred. Study 2 compared the effects of 60 and 6 ng/kg/hr ceruletide IV to those of 0.4 mg/kg/hr pentazocine IV and investigated whether these effects were naloxone reversible. Both ceruletide doses, 60 ng/kg/hr slightly more than 6 ng/kg/hr, elevated threshold and tolerance to electrically induced and threshold to thermally induced pain markedly, pentazocine acted stronger and longer than ceruletide (p<0.001). Naloxone reversed the effects of pentazocine but not of ceruletide. Conclusion: ceruletide (1) exerts potent naloxone resistant analgesic effects, which, however, are inferior to those of pentazocine, and (2) produces only mild sedation.     

Protective effect of zinc supplementation on blood antioxidant defense system in rats exposed to cadmium

The aim of this study was to assess the effects of subchronic exposure to cadmium (Cd) on the antioxidant defense system of red blood cells (RBCs) and lipid peroxide concentration in the plasma, as well as the possible protective role of zinc (Zn). For this purpose, 60 male Wistar rats (8 weeks old) were divided into three groups: the first group was exposed to Cd in the form of CdCl₂, administered in five doses (each of 0.4 mg Cd/kg BW) on days 5, 10, 15, 20 and 25, giving a total dose of 2 mg Cd/kg BW, i.p.; the second group was simultaneously exposed to Zn and Cd with the same timeline and the same doses of Cd as the first group but with, in addition, injections of Zn in the form of ZnCl₂, administered in doses of 0.8 mg Zn/kg BW, giving a total dose of 4 mg Zn/kg BW, i.p.; a control group received 0.5 mL of physiological saline in an identical manner.

It was shown that exposure to Cd induced a significant decrease (p<0.05) in superoxide dismutase (Zn/Cu SOD) and catalase (CAT) activities in RBCs. Increased lipid peroxide concentration, measured by thiobarbituric acid reactive substances (TBARS), was also observed in the plasma of cadmium-exposed rats. Cd had no effect on glutathione peroxidase (GSH-Px) activity. Zn administration had a beneficial effect on the Cd-induced decrease in Zn/Cu SOD activity (p<0.05) but not on CAT activity. Animals receiving Cd and Zn simultaneously had significantly (p<0.05) lower concentrations of lipid peroxides than rats exposed to Cd alone. Our results indicate that Cd causes oxidative stress and that Zn supply in conditions of exposure to Cd can partially protect against Cd-induced oxidative stress.     

A novel silicon complex is as effective as sodium metasilicate in enhancing the collagen-induced inflammatory response of silicon-deprived rats

An experiment was conducted with rats to determine whether silicon deprivation affects the inflammatory response to the injection of type II collagen, and to compare the effectiveness of the organic complex arginine silicate inositol (ASI) with inorganic silicon (NaSiO₃) in mitigating any observed change in response. Dark Agouti rats were fed a ground corn–casein–safflower-based diet containing about 2.8 mg Si/kg. The experimental variables were supplemental 0 and 35 mg Si/kg as either ASI or NaSiO₃. After five weeks on their respective treatments, each rat was injected with type II collagen and euthanized four weeks later. Urine was collected before injection during week five and week nine before euthanasia. The silicon-supplemented rats generally exhibited a more marked inflammatory response than the silicon-deprived rats. The circulating number of lymphocytes was higher (p<0.003) and number of neutrophils was lower (p<0.008) in silicon-deprived than silicon-supplemented rats. ASI and NaSiO₃ were about equally effective in enhancing these changes. Post-injection of tibial release of prostaglandin E₂ (PGE₂) (p<0.04), urinary excretion of magnesium (p<0.03) and deoxypyridinoline (p<0.009), and plasma osteopontin (p<0.009), magnesium (p<0.0007) and copper (p<0.004) were higher in silicon-supplemented than silicon-deprived rats. The increases in plasma magnesium (Si×sex, p<0.04) and copper (Si×sex, p<0.02) were more marked in male than female rats. One but not the other silicon supplement when compared to silicon deprivation significantly affected the tibial release of PGE₂, and plasma copper and iron concentrations. However, with the exception of the pre-injection urinary excretion of helical peptide, no other of the variables determined was significantly different between rats fed ASI and those fed NaSiO₃. The findings suggest that, in rodents, physiological amounts of silicon promote the immune response, sex may influence the response to dietary silicon, and that both organic silicon complexes and inorganic silicon are similarly effective in preventing changes in inflammation induced by silicon deprivation.     

Relationship between indices of iron status and coronary risk factors including diabetes and the metabolic syndrome in Saudi subjects without overt coronary disease

There have been inconsistent reports on the relationship between iron status and coronary artery diseases (CAD), and little data on this relationship in non-Caucasian populations.

We assessed dietary iron by questionnaire and measured serum iron and ferritin levels in 270 Saudi male subjects without established CAD, 130 of whom were angiogram negative. Serum lipid profile, glucose, high sensitivity-C reactive protein (hs-CRP), serum soluble intercellular adhesion molecules-1 (sICAM-1), and caeruloplasmin were measured in all subjects.

The angiogram negative patients, had lower serum ferritin (p<0.05) and iron (p<0.0001) levels than the 140 subjects without reported cardiovascular diseases (CVD). Serum iron correlated with serum triglycerides (p<0.0001) and total cholesterol (p<0.05) levels for this latter group and the groups combined. Serum ferritin correlated with serum total cholesterol and low-density lipoprotein (LDL)-cholesterol in the combined group (p<0.05), and was correlated with blood glucose and serum LDL-cholesterol (p<0.05) in the subjects without reported CVD. After adjustment for confounding variables, serum iron levels remained a significant correlate with total calorie intake and serum triglycerides. Serum ferritin also correlated significantly with cholesterol intake and fasting serum total cholesterol. Dietary iron was significantly related to dietary cholesterol and fiber, age, smoking habits, and serum total cholesterol level.

Hence, indices of iron status were related to several coronary risk factors in the Saudi population.     

Liquid supplementation of grazing cows and calves

One hundred and one Angus cows (average weight 614 kg) and their bull calves (average weight 213 kg) grazing improved summer pastures were used to determine cow and calf intake of liquid supplement, and its effect on forage intake and performance. Forty-seven pairs had access to a 410 g CP/kg DM molasses-based liquid supplement in an open feeder and 54 pairs were not supplemented. The study was conducted in southwestern Montana from July 28 to October 3, 1997. Cows consumed significantly more supplement (0.3 kg/day) than calves (0.1 kg/day) but both consumed 0.5 g/kg bodyweight per day. Supplemented cows gained 0.12 kg/day more (p<0.05) than unsupplemented cows; however, there was no difference (p>0.10) in body condition score change. Average daily gain by supplemented calves was 30% greater (p<0.01) than average daily gain by unsupplemented calves. Forage intake (g/kg body weight) by both supplemented cows and calves was 64% greater (p<0.01) than forage intake by unsupplemented cows and calves. There was no difference (p>0.10) in milk intake between supplemented and unsupplemented calves. There was no difference (p>0.10) in time spent at the supplement feeder between cows and calves, averaging 5.0 min/day. Time at the feeder was lowest for 7-year-old cows, intermediate for 6- and 8-year-old cows, and highest for 9-year-old cows (p<0.10). There was no difference (p>0.10) in supplement feeding bouts/day between age groups of cows. Calf liquid supplement intake (g/kg body weight) and time spent at the supplement feeder were similar to intake and time spent at the feeder by cows. Liquid supplementation increased forage intake and average daily gain by cows and calves grazing improved forages in late summer. The cost for additional weight gained by the supplemented calves was US$ 0.33/kg and October cattle prices in Montana were US$ 1.64/kg. Liquid supplementation was cost effective under the conditions of this study.     

Arginine vasotocin and aggression in rats

Pinealectomized (PX) and sham animals were administered either AVT (1 ng/kg) or vehicle (1 ml H₂O). Boxing-kicking-biting episodes were significantly reduced by administration of AVT, F(1,21)=8.09,p<0.009. Crawling under behavior was increased in PXH₂O animals (p<0.05). Non-aggressive rearing was decreased by administration of AVT, F(1,21)=4.75, p<0.04. These results are in agreement with previous findings that AVT lowers emotionality-arousal. Results are discussed in terms of vasotonergic effects on central monoamines.     

Distinct hemodynamic and gastric effects of human CGRP I and II in man

The human calcitonin gene-related peptides I and II (or and β) (CGRP I and II) are encoded by two different genes, but they have 34 of the 37 amino acid residues in common. Human CGRP I more potently stimulated blood flow through the skin and carotid artery (p<0.01), and the heart rate (p<0.05), and plasma renin activity and aldosterone secretion than human CGRP II (p<0.02). Inhibition of pentagastrin-stimulated gastric acid output, on the other hand, was only obtained with CGRP II. The separate effects of human CGRP I and II on the cardiovascular and gastric systems are presumably mediated by different receptors or receptor pathways recognized by the two closely related neuropeptides.     

Expression of angiotensin type 1 and 2 receptors in brain after transient middle cerebral artery occlusion in rats

Angiotensin II (Ang II) type 2 receptors (AT2Rs) have been associated with apoptosis. We hypothesized that AT2Rs are increased in stroke and may contribute effects of stroke to the brain. To test this, we have examined the expression of Ang II type 1 receptor (AT1R), AT2R and Ang II levels in the brain 24 h after transient middle cerebral artery occlusion (MCAO). The densities of AT1R and AT2R were measured by quantitative autoradiography (n=6). The levels of Ang II were measured by radioimmunoassay (RIA) (n=6) and by immunohistochemistry (n=3). AT1R levels on autoradiography showed a significant decrease (0.87±0.06 to 1.39±0.07 fmol/mg, p<0.01) in the ventral cortex of the stroke side compared to the cortices of non-stroke (NS) rats (n=4). There was no significant difference on ATIR in the contralateral verbal cortex of the stroke rats compared to NS control. In contrast, levels of AT2R in the ventral cortex of both the stroke and the contralateral sides were significantly increased (0.77±0.06, p<0.05 and 0.91±0.05, p<0.01 compared to 0.60±0.03 fmol/mg tissue, respectively). RIA showed that Ang II in the ventral cortex of both the stroke and the contralateral sides were significantly increased (241.63±47.72, p<0.01 and 165.51±42.59, p<0.05 compared to 76.80±4.10 pg/g tissue, respectively). Also, Ang II in the hypothalamus was significantly increased (179.50±17.49 to 118.50±6.65 pg/g tissue, p<0.05). Immunohistochemistry confirmed the increase of Ang II. These results demonstrate that brain Ang II and AT2Rs are increased whereas AT1Rs are decreased after transient MCAO in rats. We conclude that in stroke, Ang II and AT2R are activated and may contribute neural effects to brain ischemia.     

Brain peptide reverses effect of morphine on human lymphocytes

E-rosette formation by human lymphocytes incubated with sheep red blood cells (sRBC) is inhibited by morphine. We studied the ability of the opiate antagonists naloxone and Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH₂) to block this action. Active E-rosette formation by lymphocytes incubated with morphine was reduced from the control of 35.7±1.7% to 23.7±1.5% (p<0.001). Similarly, total E-rosette formation was reduced by morphine from the control of 65.8±1.3% to 53.2±2.9% (p<0.001). These effects were blocked by co-incubation of the lymphocytes with either Tyr-MIF-1 or naloxone (p<0.05). Tyr-MIF-1 was active (p<0.05) at concentrations as dilute as 10⁻¹³M. These results indicate that the neuropeptide Tyr-MIF-1 exerts an antiopiate effect at the human T-lymphocyte.     

Adaptive changes in muscular performance and circulation by resistance training with regular cold application

(1) Sixteen male subjects participated in resistance training comprising three sets of 8-handgrip exercises at a workload that could be performed no more than eight times, three times a week for 6 weeks. Eight subjects immersed their experimental forearm in cold water (10±1 °C) for 20 min following each training period, while the remaining eight served as controls. (2) Muscular endurance with rhythmic handgrips significantly (p<0.01) increased in both groups after the training period with a non-significant difference between groups. The relative diameter of ultrasonography-evaluated brachial artery failed to increase in the immersion group despite a significant increase (p<0.05) of that in the control group after training. (3) Regular post-exercise cold application might attenuate the improvement in muscular endurance, possibly in association with reduced vascular remodeling.     

Algesia and local responses induced by neurokinin A and substance P in human skin and temporal muscle

Neurokinin A (NKA), substance P (SP) and the two peptides combined (SP + NKA) were injected intracutaneously on the forearm and into the temporal muscle of healthy volunteers. Pain intensity, cutaneous wheal and flare responses and tenderness of the temporal muscle were quantitated. SP but not NKA induced cutaneous pain. This relates the algesic effect of SP to the specific N-terminal amino acid sequence of the peptide, not shared by NKA. NKA, however, potentiated the algesic effect of SP as SP + NKA induced a significantly prolonged cutaneous pain sensation. Both peptides induced wheals, but only SP induced flare. These results confirm previous studies relating wheal formation to the identical C-terminal amino acid sequence of the two peptides and flare reaction to the N-terminal part of SP. Injections into the temporal muscle did not cause pain or tenderness.     

Length-tension properties of ankle muscles in chronic human spinal cord injury

Contracture, or loss of range of motion (ROM) of a joint, is a common clinical problem in individuals with spinal cord injury (SCI). In order to measure the possible contribution of changes in muscle length to the loss of ankle ROM, the active force vs. angle curves for the tibialis anterior (TA) and gastrocnemiussoleus (GS) were measured in 20 participants, 10 with SCI, and 10 gender and age matched, neurologically intact (NI) individuals. Electrical stimuli were applied to the TA and GS motor nerves at incremented angles of the entire ROM of the ankle and the resulting ankle and knee torques were measured using a multi-axis load cell. The muscle forces of the TA and GS were calculated from the torque measurements using estimates of their respective moment arms and the resulting forces were plotted against joint angle. The force–angle relation for the GS at the ankle (GSA) was significantly shifted into plantar flexion in SCI subjects, compared to NI controls (t-test, p<0.001). Similar results were obtained based upon the GS knee (GSK) force–angle measurements (p<0.05). Conversely, no significant shift in the force–angle relation was found for the TA (p=0.138). Differences in the passive ROM were consistent with the force–angle changes. The ROM in the dorsiflexion direction was significantly smaller in SCI subjects compared to NI controls (p<0.05) while the plantar flexion ROM was not significantly different (p=0.114). Based upon these results, we concluded that muscle shortening is an important component of contracture in SCI.     

Adaptations in muscular activation of the knee extensor muscles with strength training in young and older adults

The purpose of this study was to compare the extent of muscular activation during maximal voluntary knee extension contractions in old and young individuals and to examine the effects of resistance training on muscular activation in each group. The interpolated twitch technique was used to estimate muscular activation during two pre-training baseline tests, and after two and six weeks of resistance training. Throughout the study, the older group was 30% less strong than the young group (p=0.02). The training protocol was effective in both groups with overall isometric strength gains of 30 and 36% in the older (p=0.01) and young (p<0.01) groups, respectively. 10-RM training loads increased by 66% in the old group (p<0.01) and by 77% in the young group (p<0.01) throughout training. At the first baseline test, a 2% difference in muscular activation between groups (p=0.3) did not explain the large disparity in strength. Muscular activation increased by 2% in both groups throughout training (p<0.01). Despite considerably less muscular strength in the older group, muscular activation was greater than 95% of maximum and appears to be equal in both young and older individuals. Both groups demonstrated similar but small increases in muscular activation throughout training.     

Enhanced healing of cartilaginous injuries by glucosamine hydrochloride

We investigated the restorative effect of orally administered glucosamine hydrochloride (GlcN) on the experimentally produced cartilaginous injuries in rabbits. A total of three holes in the left stifle joint including one in the medial trochlear ridge and two in the trochlear sulcus (proximal and distal) of articular cartilage were made surgically using a drill. For the control group, only tap water and for the glucosamine group, a water based solution of GlcN (1 g/head) was administered daily, respectively. We observed the clinical symptoms daily and the condition of the injured part was observed visually and histologically at 3 weeks after the operation. There was no difference in body weight or general conditions between the two groups. However, in the control group, the muscle weight of the biceps of the left femur was significantly reduced (p<0.05). With respect to the medial trochlear injury, four out of six cases in the control group and five out of six cases in the glucosamine group were cured, respectively. With respect to the proximal and the distal holes in sulcus, only two out of six cases in the control group and five expansive out of six cases in the glucosamine group were cured. There was significant difference between the glucosamine group and the control with respect to healing of the proximal hole (p<0.05) and the total points (p<0.05), indicating that the artificial cartilage injuries were facilitated by GlcN. On histological examination, the injured parts were covered by fibrous connective tissues in the control, whereas in the glucosamine group, the massive proliferation of matured cartilaginous tissues was observed, and the regenerated cartilaginous tissues were surrounded by the proliferation of chondroblast cells. In the regenerated tissue, matured cartilage substrate was about to be formed. Safranin O and alcian blue stains marked significantly dense in the glucosamine group than in the control (p<0.01) in injured parts as well as in non-injured joint cartilage.     

A preliminary study of steroid reproductive hormones in human hair

Nowadays research and clinical studies of human reproductive endocrinology are generally carried out using human blood reproductive hormone assays. However the acquisition of human blood samples has some shortcomings. In search of new approaches, we paid attention to the fact that progesterone can be detected in cow's hair. Consequently we investigated whether or not steroid hormones are measurable in human hair. The results showed that the levels of steroid hormones in hair are not affected by shampoo and do not significantly vary between different segments of hair (i.e. top, middle and basal segments). The menstrual estradiol and progesterone rhythm of female hair is similar to that of female serum. The ratio of hair estradiol to serum estradiol in the female is 41.2% and that of hair progesterone to serum progesterone is 59.0%; the ratio of hair testosterone to serum testosterone in male is 116%. There are significant correlations between hair and serum steroid hormones of healthy human adult: γ (estradiol)=0.395 (n=20), p<0.05; γ (progesterone)=0.440 (n=22), p<0.025 and γ (testosterone)=0.395 (n=25), p<0.05.     

Elevated breath pentane in heart failure reduced by free radical scavenger

Pentane, a product of lipid peroxidation, has been detected in situations involving ischemic injury. Such injury may be limited if lipid peroxidation can be controlled by antioxidants. The role of lipid peroxidation in chronic heart failure (CHF) was assessed by measuring breath pentane in patients with CHF vs. age matched controls. The effect of a free radical scavenger on pentane released during CHF was also measured. Pentane levels were correlated with the daily dose of captopril, a sulfhydril-containing drug used to treat CHF, which is an angiotensin converting enzyme inhibitor. To separate the scavening effects of captopril from the pharmacologic effects of converting enzyme inhibitors, a crossover study using a nonsulfhydril inhibitor was used. Patients with CHF excreted (p < 0.005) hich concentrations of pentane (5.7 ± 2.1 vs. control 3.6 ± 1.2 nmol/l). Patients treated with captopril also had significantly higher (p < 0.05) excretion of pentane than the control patients (4.7 ± 1.3 vs. 3.6 ± 1.2 nmol/l). The dose of captopril was inversely proportional to the concentration of pentane excreted (r = 0.55, p < 0.05). Pentane excretion during captopril therapy was significantly lower before (p < 0.01) and after (p < 0.02) nonsulfhydril inhibitor therapy. Conclusion: breath pentane is elevated in CHF and it can be reduced by a free radical scavenger. This reduction of pentane excretion is not a converting enzyme inhibitor class effect.     

Knoop microhardness anisotropy of the ovine radius

The Knoop indenter has been used to characterise fully the Knoop microhardness (H_K) anisotropy of compact bone. 2120 indentations were performed on mature ovine radii and a linear relationship was found between H_K and the angle between the major diagonal of the indenter and the lamella boundaries (p0.001). H_K increased significantly with ash fraction (p0.001), but decreased with atmospheric vapour pressure (p<0.05). A significant interaction was found between ash fraction and atmospheric vapour pressure (p<0.01). H_K significantly varied with indentation position along the diaphysis and around the cortex (both p0.001), however radial variation in H_K was not statistically significant. The variation of ash fraction showed similar trends. These data show that H_K varies similarly to Vickers microhardness, but in addition, can provide clear information on the anisotropy of Haversian bone without the need for excising many different indentation planes. A large number of indentations are required to obtain low type I and type II errors in the statistical analysis.