Retinoids, 585-nm laser, and carbon dioxide laser: a numeric comparison of neocollagen formation in photoaged hairless mouse skin.

BACKGROUND: A variety of new methods for treating photoaging have been recently introduced. There has been increasing interest in comparing the relative efficacy of multiple methods for photoaging. However, the efficacy of a single method is difficult to assess from the data reported in the literature. METHODS: Photoaged hairless mice were randomly divided into seven treatment groups: control, retinoids (tretinoin and adapalene), lasers (585 nm and CO(2)), and combination groups (585 nm + adapalene and CO(2 )+ adapalene). Biopsies were taken from the treated regions, and the results were analyzed based on the repair zone. The repair zones of the various methods for photoaging were compared. RESULTS: Retinoids produced a wider repair zone than the control condition. The 585-nm and CO(2) laser resurfacing produced a result equivalent to that of the control condition. A combination of these lasers with adapalene produced a wider repair zone than the lasers alone, but the combination produced a result equivalent to that of adapalene alone. CONCLUSION: Retinoids are potent stimuli for neocollagen formation. The 585-nm or CO(2) laser alone did not induce more neocollagen than the control condition. In addition, no synergistic effect was observed with the combination treatments. The repair zone of the combination treatment is mainly attributable to adapalene.

Efficacy of pulsed electromagnetic therapy for chronic lower back pain: a randomized, double-blind, placebo-controlled study.

This randomized, double-blind, placebo-controlled clinical trial studied the effectiveness of pulsed electromagnetic therapy (PEMT) in patients with chronic lower back pain. Active PEMT (n = 17) or placebo treatment (n = 19) was performed three times a week for 3 weeks. Patients were assessed using a numerical rating scale (NRS) and revised Oswestry disability scores for 4 weeks after therapy. PEMT produced significant pain reduction throughout the observation period compared with baseline values. The percentage change in the NRS score from baseline was significantly greater in the PEMT group than the placebo group at all three time-points measured. The mean revised Oswestry disability percentage after 4 weeks was significantly improved from the baseline value in the PEMT group, whereas there were no significant differences in the placebo group. In conclusion, PEMT reduced pain and disability and appears to be a potentially useful therapeutic tool for the conservative management of chronic lower back pain.

Risk of betel chewing for oesophageal cancer in Taiwan.

Among 104 cases of squamous-cell oesophageal carcinoma patients and 277 controls in Taiwan, after adjusting for cigarette smoking, alcohol consumption, and other confounders, we found that subjects who chewed from 1 to 495 betel-year and more than 495 betel-years (about 20 betel quid per day for 20 years) had 3.6-fold (95% Cl = 1.3-10.1) and 9.2-fold risk (95% Cl = 1.8-46.7), respectively, of developing oesophageal cancer, compared to those who did not chew betel.

Anticonvulsive and free radical scavenging activities of Gastrodia elata Bl. in kainic acid-treated rats.

Gastrodia elata Bl. (GE) is a traditional Chinese herb that is commonly used in Chinese communities to treat convulsive disorders such as epilepsy. The purpose of the present study was to determine the anticonvulsive and free radical activities of GE in rats. In vitro studies were conducted by using brain tissue from 6 male Sprague-Dawley (SD) rats treated with 120 microg/ml of kainic acid (KA), with or without the addition of various concentrations of GE. In vivo studies were conducted in a total of 30 male SD rats divided into 5 groups of 6 rats which were treated as follows: 1) the normal group received an intraperitoneal injection (i.p.) of PBS (Phosphate buffer saline, 1 ml/kg); 2) the control group received KA (12 mg/kg) i.p.; 3) the GE 1.0 group received oral administration of GE 1.0 g/kg 30 min prior to KA administration; 4) the GE 0.5 group received oral administration of GE 0.5 g/kg 30 min prior to KA administration; 5) the PH group received oral administration of phenytoin 20 mg/kg 30 min prior to KA administration. Seizures were verified by behavioral observations, electroencephalograph (EEG) and electromyography (EMG). Lipid peroxide levels in the rat brain, luminol chemiluminescence (CL) and lucigenin-CL in the peripheral blood were measured simultaneously after behavioral observations. The results indicate that GE administration significantly reduced KA-induced lipid peroxide levels in vitro. Oral administration of GE 1.0 g/kg and phenytoin 20 mg/kg significantly reduced counts of wet dog shakes (WDS), paw tremor (PT) and facial myoclonia (FM) in KA-treated rats. In addition, oral administration of GE 1.0 g/kg significantly delayed the onset of WDS, from 30 min in the control group to 46 min in the 0.5 g/kg group, and 63 min in the GE 1.0 g/kg group. A significantly reduced level of lipid peroxides in the rat brain was found in the GE 1.0 g/kg, 0.5 g/kg, and phenytoin 20 mg/kg groups. The GE 1.0 g/kg group showed significant reduction of luminol-CL and lucigenin-CL counts in the peripheral blood compared to the control group. The results of the present study demonstrate that GE has anticonvulsive and free radical scavenging activities. Further studies are needed to determine the clinical effectiveness of GE as an anticonvulsant in humans.

Ovarian expression of melatonin Mel(1a) receptor mRNA during mouse development.

Melatonin, secreted by the pineal gland, is involved in the regulation of many physiological functions of various species of animals. In the present study, the expression of gene for melatonin Mel(1a) receptor (MelR) was evaluated in the ovary, hypothalamus, and pituitary according to the developmental stages in female mice. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) and in situ PCR techniques were applied. According to the developmental stages, gene for MelR was differently expressed on ovary, hypothalamus, and pituitary. MelR gene was first expressed on pituitary prior to the expression in hypothalamus and ovary. Ovarian MelR gene started to express at birth. Unlike hypothalamic expression of MelR gene which was identified after birth, in pituitary, it was expressed at 16 days post coitum. In the ovary, the expression signal of MelR gene was identified on granulosa cells. However, the signal was not detected in the theca cells. It was weak in the primordial and atretic follicles. Taken together, it can be considered that melatonin has a pivotal role in the folliculogenesis.

Genetic polymorphisms of XRCC1 and risk of the esophageal cancer.

A variety of environmental factors were identified to be associated with the risk of esophageal cancer. The variation in capacity of DNA repair might influence environmental chemical-associated carcinogenesis. We hypothesized that the polymorphic XRCC1 genes might modify cancer susceptibility of the esophagus. To investigate the effect of XRCC1 genetic polymorphisms on codons 194, 280 and 399, we evaluated data from 105 patients of esophageal squamous cell carcinoma and 264 healthy controls, matching with age (+/-3 years), gender and ethnicity. The distribution of the 3 genotypes were not significantly different among patients and controls. However, among alcohol drinkers, the XRCC1399 Arg/Arg genotype was more frequently found in patients with esophageal cancer. After adjustment with other environmental confounders, the OR for the genotype of XRCC1399 Arg/Arg was 2.78 (95% CI =1.15-6.67) as compared with the XRCC1(399) Arg/Gln and XRCC1(399) Gln/Gln genotypes in the alcohol drinkers. Similar trends were observed among cigarette smokers and areca chewers. However, they did not reach a statistical significance. Our findings suggest that the polymorphic XRCC1 genes might modify the risk of alcohol-associated esophageal cancers.

Analgesic effect of electric stimulation of peripheral nerves with different electric frequencies using the formalin test.

Although electroacupuncture (EA) has been widely used to treat pain, the optimal frequency of EA therapy remains unclear. The study sought to determine the effect of different EA frequencies in a Sprague-Dawley (SD) rat model of pain. Electric stimulation (ES) at frequencies of 2 Hz, 15 Hz or 100 Hz was applied to the ipsilateral or contralateral sciatic nerve of the injected hindpaw of SD rats. Formalin (50 microl, 5%) was subcutaneously injected into the plantar surface of the left hindpaw to induce a nociceptive response. Behavior, including licking and biting, was observed to have two distinct periods, an early phase during the first 5 mins and a late phase from 21-35 mins after injection. The total biting or licking count served as an Indicator of nociceptive response. Our results indicate that ES of the ipsilateral sciatic nerve at a frequency of 2 Hz or 15 Hz reduced the nociceptive responses in both the early and the late phases of the formalin test, whereas ES at 2 Hz had greater antinociceptive effect than ES at 15 Hz in the early phase. No similar analgesic effect in the early phase was observed for ES at 100 Hz. Both pretreatment with ES at 2 Hz and naloxone (3 mg/kg, s.c.) produced a greater antinociceptive response in the late phase than when ES at 2 Hz was delivered immediately after formalin administration. In addition, ES of the neck muscle or contralateral sciatic nerve at a frequency of 2 Hz also decreased licking and biting activity in both phases. The results of this study indicate that different analgesic mechanisms are involved in the response to ES at frequencies of 2 Hz, 15 Hz and 100 Hz, and that ES at 2 Hz has a greater analgesic effect on formalin-induced nociceptive response, especially when it is delivered prior to the onset of pain. The analgesic effect of ES may be mediated via a central origin in the supraspinal level. These findings suggest that 2 Hz may be a good frequency selection for clinical EA applications in analgesia, and that pretreatment with EA at 2 Hz may be an effective method to treat post-operative pain.

Reduction of electrically evoked neural activity by ginseng saponin in rat hippocampal slices.

It is well established that ginseng saponin has positive influences on various neural diseases, but little is known about its electrophysiological effects in the central nervous system. In this study, we examined the electrophysiological effects of ginseng saponin in rat hippocampal slices. Total saponin from ginseng root reduced the slope of fEPSPs (field excitatory postsynaptic potentials) in the CA1 area in a dose-dependent manner (9.1 +/-5.4%, 48.4+/-12.1%, and 60.5+/-15.3% at 10, 50, and 100 microg/ml, respectively), which was reversed within 10 min of washout. Seven different ginsenosides resulted in varied degrees of fEPSPs reduction. The rank order of reduction was Rb1, Rg1 >Rg2, Rh1, Rc>Rd, Re within a range of 5-64% reduction. No difference in the suppressive action between protopanaxadiol (Rb1, Rc, Rd) and protopanaxatriol (Rg1, Rg2, Re, Rh1) saponins was shown; the slope of fEPSPs was reduced by 38% and 40% on average, respectively. The possible role of gamma-aminobutyric acid (GABA(A)) receptor in the suppressive action of ginseng saponins was tested using whole cell patch recording in acutely isolated hippocampal neurons. Ginsenosides did not induce chloride current nor modified GABA-induced current. Also, the suppressive effect of ginsenosides on fEPSPs was still observed in the presence of the GABA(A) receptor antagonist, bicuculline methiodide 50 microM. These results suggest that the suppressive effect is not attributable to regulation of GABA(A) receptor activation.

Possible involvement of norepinephrine transporter activity in the pulsatility of hypothalamic gonadotropin-releasing hormone release: influence of the gonad.

Pulsatile secretion of hypothalamic gonadotropin-releasing hormone (GnRH) is suppressed by alpha-adrenergic antagonists in ovariectomized (OVX) rabbits, thus suggesting that initiation of GnRH pulses requires the presence of norepinephrine (NE) stimulation. Terminals of NE neurons are located in proximity with GnRH cells in the hypothalamus, including the arcuate nucleus-median eminence (AME) region. Synaptic NE molecules may be catabolized or transported back to NE terminals (i.e. reuptake) via specific NE transporter proteins (NET). Thus, the amount of synaptic NE acting on GnRH cells is a function of the rate of NE release, metabolism and reuptake. Hypothetically, the rise and fall of a GnRH pulse may be associated with the similar fluctuations of synaptic NE release and/or NET activity. To test this hypothesis, we examined the effects of AME administration of desipramine (DMI, a specific NET blocking drug) on GnRH release. First, we delivered 0.2-10 mM doses of DMI continuously for 1 h via an AME microdialysis (microD) system into intact male rabbits. We found that each AME-DMI infusion, between dosages of 1 mM and 10 mM, stimulated a GnRH pulse, and that the size of these GnRH pulses were proportional to the dosage of DMI. To confirm the specificity of DMI on NET, we measured catecholamine content in microD samples by HPLC. The temporal (60 min) DMI induced a pattern of NE release that included a rising limb within the first 20-30 min; although NE returned to baseline values within the period of DMI treatment. Neither epinephrine nor dopamine levels were changed by DMI. Second, a median dose of DMI (5 mM) was given by microD for 60 min in four separate rabbit models: gonadal intact females (F-INT), intact males (M-INT), gonadectomized females (F-GDX) and castrated males (M-GDX). Individual microD samples were measured for NE and GnRH. Regardless of gender or gonadal status, 5 mM of DMI concomitantly induced a pulse-like release of NE and GnRH. Furthermore, the response of GnRH to DMI was greater in GDX rabbits than in INT animals of both genders. Third, we administered DMI (5 mM) for 30 min via a push-pull perfusion (PPP) system during four repeated 90 min intervals, in either F-INT or ovariectomized (F-GDX) females, and measured GnRH in PPP samples. In both F-INT and F-GDX, each DMI challenge induced a GnRH pulse. In F-INT, all sequential DMI-induced GnRH pulses were nearly equal in size. In contrast, in F-GDX, the first DMI-induced GnRH pulse was greater than subsequent ones. Collectively, these observations are consistent with the concept of noradrenergic regulation of pulsatile GnRH release, and we conclude that the temporal activity of NET may be an integral part of the mechanism by which GnRH pulses operate.

Characterization of hemin binding activity of Streptococcus pneumoniae.

Streptococcus pneumoniae is a causative agent of bacterial pneumonia, otitis media, meningitis, and bacteremia. It causes considerable morbidity and mortality throughout the world, especially among children, the elderly, and immunocompromised individuals. We have demonstrated previously that the growth of S. pneumoniae is limited under iron-depleted conditions and can be restored by the addition of either hemin or hemoglobin. In the present study, we showed that S. pneumoniae had the ability to bind hemin and that the level of hemin binding activity was not affected by supplementation of the growth medium with iron. Approximately 70 to 80% of the hemin binding activity was mediated by proteinase-resistant components, and the remainder was mediated by proteins. Hemin binding proteins were located in both soluble extract and envelope fractions of pneumococcal cells. By batch affinity chromatography, a major hemin binding polypeptide with an apparent molecular mass of 43 kDa was identified in the cell lysate of S. pneumoniae. Polyclonal antibodies against this polypeptide were raised. By immunoblot analysis, this hemin binding polypeptide was localized in the envelope and did not exhibit any variation in molecular weight among all serotypes tested. The subcellular distribution of hemin binding activity may have functional implications.

Delayed presentation of cerebral arterial gas embolism following proven intraoperative venous air embolism.

We describe the case of a 33-year-old woman who suffered a delayed-onset arterial gas embolism following a significant venous air embolism during surgery to remove an acoustic neuroma. We report the management of the problem and discuss the mechanisms by which this event might have occurred.

Alteration of cerebral microcirculation by hemodilution with hemosome in awake rats.

Our study showed that hemodilution with modified fluid gelatin resulted in an increase in local cerebral blood flow (LCBF), but no change at all in local cerebral oxygen delivery (LCOD) in rats. Hemosome, a lecithin encapsulated hemoglobin having the oxygen-carrying capacity, was developed to improve LCOD by hemodilution. Therefore, we have hypothesized that LCBF & LCOD would be increased by hemodilution with hemosome. To test this hypothesis, adult male Sprague-Dawley rats weighing approximately 350g were used and divided into the hemodilution and the control groups. Hemosome was made from pig red blood cells and lecithin. It's mean diameter was approximately 0.3 um and hemoglobin concentration was approximately 4g/dl. Isovolemic hemodilution, which lowered the systemic hematocrit from approximately 50% to approximately 30%, was achieved by rapidly replacing blood with the same volume of hemosome. Ten min later, LCBF in 14 brain structures were measured using the 14C-iodoantipyrine technique. Our results showed that LCBF of the control group ranged from 115 +/- 11 ml/100g/min in the medulla to 260 +/- 31 ml/100g/min in the occipital cortex. LCBFs were generally higher (p < 0.05, MANOVA) by 16% in the hemodilution group than in the control group. However LCODs were generally decreased (p < 0.05, MANOVA) by 18% in the hemodilution group than in the control. In conclusion, hemodilution with hemosome indeed improves LCBF but lowers LCOD in awake rats.

Postnatal development of GABAA receptor function in somatosensory thalamus and cortex: whole-cell voltage-clamp recordings in acutely isolated rat neurons.

GABAergic inhibition synchronizes oscillatory activity in the thalamocortical system. To understand better the role of this neurotransmitter in generation of thalamocortical rhythmicity, the postnatal development of GABAergic function mediated through activation of GABAA receptors was studied in thalamus and cortex. GABA-evoked chloride currents were recorded in dissociated rat cortical and thalamic neurons during postnatal development. Kinetic fits of GABA concentration/response relationships revealed developmental and regional alterations in the potency of GABA. Early in postnatal development (p5-p8), both thalamic and cortical neurons exhibited reduced potency of GABA (27-31 microM KD). Potency increased by p18-p25 in thalamic and cortical neurons (19-22 microM KD), to a level maintained in adult thalamic neurons. Adult cortical neurons exhibited reduced potency of GABA (40 microM KD). Benzodiazepine modulation of GABAA currents was also studied. Kinetic analyses of benzodiazepine augmentation of GABAA currents were best fitted assuming two effective sites with different affinities for clonazepam. The high-affinity site (KD of 0.05-0.27 nM) showed little variation with development in cortical neurons, contributing about 16-23% potentiation at all postnatal ages. Developing thalamic neurons (p5-p25) showed similar potency and efficacy of the high-affinity benzodiazepine site to cortical neurons. High-affinity benzodiazepine effects disappeared in adult thalamic neurons. A lower-affinity benzodiazepine site (25-50 nM KD) was greater in efficacy in cortical neurons compared to thalamic neurons at all ages, with efficacy ranging from 50% to 110% in cortex and from 20% to 60% in thalamus. Knowledge of developmental and regional alterations in GABAA receptor function may aid in understanding mechanisms involved in generation and control of normal and pathological thalamocortical rhythms.

Photodynamic therapy using m-tetra(hydroxyphenyl) chlorin. An animal model.

OBJECTIVE: To evaluate the potent photosensitizer m-tetra (hydroxyphenyl) chlorin (m-THPC) by using rabbits with cottontail rabbit papillomavirus-induced tumors and the canine larynx as model systems. DESIGN: Nonrandomized control trial. SETTING: Division of ear, nose, and throat research at a tertiary care teaching hospital. MATERIALS: Rabbits were used for relative retention ratio studies and tissue tolerance tests. Studies on the swelling of normal tissues in the larynx after photoactivation were done with canines. INTERVENTION: Animals were injected with 0.3 mg/kg of m-THPC. At varying intervals, tissues were exposed to 652 nm of light. OUTCOME MEASURES: Outcome measures consisted of four elements: (1) decay of plasma concentration over time, (2) interval to and duration of maximal ratio between drug concentration in normal tissue and tumor, (3) maximal permissible light exposure to normal tissue (skin and laryngeal mucosa) at an optimal interval, and (4) efficacy--number of tumors with partial and complete response. RESULTS: The largest papilloma to skin ratio (10:1) occurred 4 to 8 days after drug injection. The rabbit skin damage threshold was 40 to 60 J/cm2 at 6 days. The canine laryngeal edema and erythema thresholds were 50 to 70 J. A 75% cure rate of papillomas was achieved with tumors that were less than 100 mm2 in area at light doses that ranged from 25 to 75 J/cm2. CONCLUSIONS: m-THPC shows efficacy in treating papilloma virus-induced tumors. We present a protocol for rapid optimization of the factors required for tumor destruction with minimal normal tissue damage, thus permitting determination of an optimal therapeutic protocol for any photosensitizer.

Thalamocortical rhythm generation in vitro: extra- and intracellular recordings in mouse thalamocortical slices perfused with low Mg2+ medium.

Mouse thalamocortical slices maintain synaptic connections between thalamus and cortex. When perfused with low Mg2+ medium, thalamocortical slices exhibited spontaneous thalamocortical 2-6 s long bursts of rhythmic activity every 15-30 s, which was potentiated by pentylenetetrazol and abolished by severing thalamocortical connections. These oscillations were similar in frequency and duration to normal and pathological thalamocortical rhythms in vivo. In vitro studies of these thalamocortical rhythms may prove valuable in understanding cellular factors important in rhythm generation.

Selective effect of chronic lead ingestion. II: Effect on phenylethanolamine N-methyltransferase activity in brain regions of rats.

Selectivity of lead effect to phenylethanolamine N-methyltransferase (PNMT) activity in regions of brain from rats postnatally exposed to lead was tested. Three groups of animals were prepared; (1) Rats exposed to lead at a low dose (0.05% PbAcetate: PbAc); (2) Rats exposed to lead at a high dose (0.2% PbAc); (3) Age-matched normal control rats. At 2, 4, 6 and 8 weeks of age weight of whole brain and body in each group were measured. At the same ages activities of PNMT and Na+/K(+)-ATPase were examined on 4 brain regions of each animal. Exposure of rats to lead generally decreased activity of Na+/K(+)-ATPase and showed alternative change of those of PNMT. Brain regions where changes of PNMT activity were detected without concomitant changes of Na+/K(+)-ATPase activity, were telencephalon and pons/medulla at 2 weeks of age and telencephalon at 4 weeks of age in rats exposed to lead at a low dose, and those in rats exposed to lead at a high dose were pons/medulla at 8 weeks of age. These data imply that adrenergic nervous system in the brain regions described above could selectively be affected by lead.

Evaluation of the indices of retinol and alpha-tocopherol status in free-living elderly.

The relationship between plasma vitamins and lipids was determined in volunteers (N = 131; age = 73.1 +/- 6.1 y). The 24-hour food intake data and fasting plasma retinol and alpha-tocopherol (HPLC), cholesterol, and triglycerides were determined three times in one year; 30 and 37% of elderly subjects had retinol and tocopherol intakes below two-thirds RDA, respectively; 35% used vitamin supplements. Plasma levels were: retinol = 1.76 +/- 0.41 mumol/L and tocopherol = 22.61 +/- 0.68 mumol/L; cholesterol = 5.15 +/- 0.77 mmol/L; triglycerides = 1.63 +/- 0.87 mmol/L. Plasma vitamin levels were adjusted to average plasma cholesterol (5.6 mmol/L) and triglyceride (1.24 mmol/L). Diet plus supplemental tocopherol intake correlated with plasma tocopherol (p less than .003). Using plasma vitamin levels, retinol status was normal, whereas 70% had low tocopherol status. Ratio of plasma alpha-tocopherol to lipids indicated that only 1-2% had low tocopherol status, while that of lipid-adjusted alpha-tocopherol to plasma lipids showed that 12% had low status. The latter ratio may be a better index of status.

Multifocal atrial tachycardia as a prognostic indicator in patients with severe chronic obstructive pulmonary disease requiring mechanical ventilation.

The records of 121 patients admitted to the Medical Intensive Care Unit (MICU) of Chang Gung Memorial Hospital with severe chronic obstructive pulmonary disease (COPD) requiring mechanical ventilation were reviewed retrospectively. Eighty-seven percent (20/23) of the patients with multifocal atrial tachycardia (MAT) expired during their ICU admission in contrast to 23.5% (23/98) of those without MAT. The only differences between these two groups were incidence of cor pulmonale, and right axis deviation, right bundle branch block, pulmonale P in electrocardiogram. MAT might be considered as a grave prognostic sign in patients with COPD severe enough to require mechanical ventilation.

Effects of supplementation of the diets with calcium and calcium-rich foods on bone density of elderly females with osteoporosis.

Diets of 20 elderly females with osteoporosis were supplemented daily with 2.25 oz of processed cheese, and 3 capsules of dicalcium phosphate + vitamin D containing 350 mg Ca, 270 mg P, and 399 IU vitamin D, for a 6-month period. The bone density of the 3-2 phalanx was measured densitometrically from the hand x-ray taken with a standard aluminum stepwedge. Fasting blood and urine were analyzed at the beginning and end of the experimental period. The mean bone density increased (p less than 0.05). There were 11 subjects with increased bone density, three with no changes and six with reductions in bone density. Calcium, P, and alkaline phosphatase in serum and Ca/creatinine and P/creatinine in urine were unchanged. The changes in bone density were correlated to the changes in body weight (r = 0.6529). The results suggested that, even with a mean age of 70 yr, some elderly persons can benefit from supplementary Ca and Ca-rich foods to improve bone density.