Environmentally induced disorders of the musculoskeletal system

The human suffering and economic cost attributable to musculoskeletal disorders cannot be overemphasized. Biomechanical principles have been introduced to explain the microtrauma and macrotrauma as mechanisms of injury. Stress-induced remodeling is a useful paradigm in the study of environmentally induced disorders. The concept of environment should include psychosocial and organizational factors with respect to musculoskeletal complaints and chronic pain. Low back pain, osteoarthritis, osteoporosis and its associated fractures, and cumulative trauma disorders are the most critical and common musculoskeletal disorders. The risk factors for low back pain have been identified, and preventive measures for reducing the chronicity of low back pain have been discussed. Preventive approaches to control or limit the fractures associated with osteoporosis and loss of bone mass are preferred to simple management of the fracture of osteoporotic patients. It can be concluded that too little or too much stress can disturb the homeostatic or the equilibrium state of health and that much remains to be researched to quantify the optimal stress levels.     

Suppression of C-Terminal Telopeptide in Hypovitaminosis D Requires Calcium as Well as Vitamin D

We compared the effects of oral calcium and vitamin D separately and together on relevant variables in 22 postmenopausal volunteers with initial serum 25OHD levels below 60 nmol/L. Subjects were allocated randomly to two regimens: group 1 received 1 week of calcium 1,000 mg, followed by 7 weeks with additional vitamin D₃ 1,000 i.u. daily; group 2 received 7 weeks of D₃ 1,000 i.u. daily, followed by 1 week with additional calcium 1,000 mg. We measured serum calcium, phosphate, PTH, 25OHD, CTX, and ALP at baseline and after 1 and 8 weeks in group 1 and after 7 and 8 weeks in group 2. There were no significant changes in ALP from either vitamin D or calcium. Calcium caused significant elevation of serum 25OHD as well as major suppression of serum CTX, which could not easily be accounted for by suppression of PTH. Vitamin D caused no significant change in any variable except elevation of serum 25OHD. The suppressive effect of calcium (whether given first or second) on serum CTX was threefold greater than that of vitamin D (whether given first or second) (P < 0.001), although their suppressive effects on serum PTH were the same. Calcium and vitamin D yielded greater and more significant effects on all variables (except ALP) than either treatment alone. We suggest that calcium may elevate serum 25OHD by prolonging its half-life and that it may have an inhibitory effect on bone resorption independent of, or in addition to, its suppression of PTH.     

A population-based survey of the epidemiology of symptom-defined gastroesophageal reflux disease: the Systematic Investigation of Gastrointestinal Diseases in China

Background

Hepatitis B immune globulins (HBIG) in combination with nucleos(t)ide analogues (NA) are effectively used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, associated treatment costs for HBIG are exceedingly high.

Methods

Fresh frozen plasma obtained from blood donors with high anti-HBs levels (hyperimmune plasma, HIP) containing at least 4,500 IU anti-HBs was used as alternative treatment for HBV recurrence prophylaxis post-LT.

Results

Twenty-one HBV-related LT recipients received HIP starting at transplantation, followed by long-term combination treatment with NA. Mean follow-up time was 4.5 years (range 0.5-12.6) and each patient received on average 8.2 HIP per year (range 5.8-11.4). Anti-HBs terminal elimination kinetic after HIP administration was 20.6 days (range 13.8-30.9), which is comparable to values reported for commercial HBIG products. All 21 patients remained free of HBV recurrence during follow-up and no transfusion-transmitted infection or other serious complication was observed. Seven patients developed reversible mild transfusion reactions. The cost for one HIP unit was US$140; average yearly HBIG treatment cost was US$1,148 per patient, as compared to US$25,000-100,000 for treatment with commercial HBIG.

Conclusion

The results of this study suggest that the use of HIP may be a useful and economical approach for the prevention of HBV recurrence post-LT if used in combination with NA. Additional prospective controlled studies in larger populations are needed to confirm these results.     

Antinociceptive activity of a synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone, on nociception-induced models in mice

Abstract: This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6‐bis‐(4‐hydroxy‐3‐methoxybenzylidene)cyclohexanone (BHMC), using chemical‐ and thermal‐induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose‐related inhibition in the acetic acid‐induced abdominal constriction test in mice with an ID₅₀ of 0.15 (0.13–0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin‐induced paw licking test with an ID₅₀ of 0.35 (0.27–0.46) mg/kg and 0.07 (0.06–0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot‐plate test. Moreover, the antinociceptive effect of the BHMC in the formalin‐induced paw licking test and the hot‐plate test was antagonized by pre‐treatment with the non‐selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID₅₀ of 0.66 (0.41–1.07) mg/kg and 0.42 (0.38–0.51) mg/kg, respectively. Finally, it was also shown that BHMC‐induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators.     

Cutaneous human papillomaviruses found in sun-exposed skin: Beta-papillomavirus species 2 predominates in squamous cell carcinoma

BACKGROUND: A spectrum of cutaneous human papillomaviruses (HPVs) is detectable in nonmelanoma skin cancers, as well as in healthy skin, but the significance that the presence of these types of HPV DNA has for the pathogenesis of skin cancer remains unclear. METHODS: We studied 349 nonimmunosuppressed patients with skin lesions (82 with squamous cell carcinomas, 126 with basal cell carcinomas, 49 with actinic keratoses, and 92 with benign lesions). After superficial skin had been removed by tape, paired biopsy samples--from the lesion and from healthy skin from the same patient--were tested for HPV DNA. Risk factors for HPV DNA were analyzed in multivariate models. RESULTS: Overall, 12% of healthy skin samples were positive for HPV DNA, compared with 26% of benign lesions, 22% of actinic keratoses, 18% of basal cell carcinomas, and 26% of squamous cell carcinomas. HPV DNA was associated with sites extensively exposed to the sun, both for the lesions (odds ratio [OR], 4.45 [95% confidence interval {CI}, 2.44-8.11]) and for the healthy skin samples (OR, 3.65 [95% CI 1.79-7.44]). HPV types of Beta-papillomavirus species 2 predominate in squamous cell carcinomas (OR, 4.40 [95% CI, 1.92-10.06]), whereas HPV types of Beta-papillomavirus species 1 are primarily found in benign lesions (OR, 3.47 [95% CI, 1.72-6.99]). CONCLUSIONS: Cutaneous HPV types are primarily detected at sites extensively exposed to the sun. HPV types of Beta-papillomavirus species 2, but not of species 1, are associated with squamous cell carcinoma.     

Antinociceptive effect of the essential oil of Zingiber zerumbet in mice: possible mechanisms

Ethnopharmacological relevance

Zingiber zerumbet (L.) Smith, a wild edible ginger species or locally known as “lempoyang”, commonly used in the Malays traditional medicine as an appetizer or to treat stomachache, toothache, muscle sprain and as a cure for swelling sores and cuts.

Aim

The present study was conducted to investigate the possible mechanism of actions underlying the systemic antinociception activity of the essential oil of Zingiber zerumbet (EOZZ) in chemical-induced nociception tests in mice.

Materials and methods

Acetic acid-induced abdominal constriction, capsaicin-, glutamate- and phorbol 12-myristate 13-acetate-induced paw licking tests in mice were employed in the study. In all experiments, EOZZ was administered systemically at the doses of 50, 100, 200 and 300 mg/kg.

Results

It was shown that EOZZ given to mice via intraperitoneal and oral routes at 50, 100, 200 and 300 mg/kg produced significant dose dependent antinociception when assessed using acetic acid-induced abdominal writing test with calculated mean ID₅₀ values of 88.84 mg/kg (80.88-97.57 mg/kg) and 118.8 mg/kg (102.5-137.8 mg/kg), respectively. Likewise, intraperitoneal administration of EOZZ at similar doses produced significant dose dependent inhibition of neurogenic pain induced by intraplantar injection of capsaicin (1.6 μg/paw), glutamate (10 μmol/paw) and phorbol 12-myristate 13-acetate (1.6 μg/paw) with calculated mean ID₅₀ of 128.8 mg/kg (118.6-139.9 mg/kg), 124.8 mg/kg (111.4-139.7 mg/kg) and 40.29 (35.39-45.86) mg/kg, respectively. It was also demonstrated that pretreatment with l-arginine (100 mg/kg, i.p.), a nitric oxide precursor significantly reversed antinociception produced by EOZZ suggesting the involvement of l-arginine/nitric oxide pathway. In addition, methylene blue (20 mg/kg, i.p.) significantly enhanced antinociception produced by EOZZ. Administration of glibenclamide (10 mg/kg, i.p.), an ATP-sensitive K⁺ channel antagonist significantly reversed antinociceptive activity induced by EOZZ.

Conclusion

Together, the present results suggested that EOZZ-induced antinociceptive activity was possibly related to its ability to inhibit glutamatergic system, TRPV1 receptors as well as through activation of l-arginine/nitric oxide/cGMP/protein kinase C/ATP-sensitive K⁺ channel pathway.     

Probiotic therapy to men with incipient arteriosclerosis initiates increased bacterial diversity in colon: A randomized controlled trial

ObjectiveThis study aimed to clarify the microbial change in the intestinal microbiota in patients, with cardiovascular disease, consuming a drink with high numbers of live Lactobacillus plantarum.MethodsSixteen males, with atherosclerotic plaque on the carotid wall, were randomly selected from a larger cohort and included in this double blind, placebo controlled study. Colonic biopsies, taken before and after four weeks of probiotic treatment, were analysed with Terminal Restriction Fragment Length Polymorphism, including digestion with MspI and HaeIII. Microbial diversity was calculated, short-chain fatty acids in faeces, and blood markers were analysed.ResultsConsumption of one probiotic strain of L. plantarum (DSM 9843) increased intestinal microbial diversity. The probiotic group had an increased diversity after consumption of the probiotic drink compared to the change in the placebo group when Shannon and Weaner diversity index (MspI and HaeIII, p = 0.026) and Simpson index of diversity (MspI, p = 0.044 and HaeIII, p = 0.026) were calculated. The fermentation pattern of short-chain fatty acids in faeces were unaffected for most acids, but the probiotic group had decreased concentration of isovaleric acid (p = 0.006) and valeric acid (p = 0.029). Viable count of lactobacilli increased in the probiotic group (p = 0.001), but no significant changes in blood markers were observed.ConclusionAdministration of a single-strain probiotic increases the bacterial diversity in the gut, and affects the concentration of some short-chain fatty acids. Consumption of the single strain L. plantarum DSM 9843 might be a strategy to favour a diverse intestinal microbiota, which is beneficial for the host.     

癌症化学预防的分子靶标

乙肝病毒和人乳头状瘤病毒分别是肝细胞癌和子宫颈癌的风险因素,针对这2种病毒感染的疫苗已在临床上成功用于癌症化学预防。分子靶向药物能够预防乳腺癌（雷洛昔芬与他莫昔芬）、大肠腺瘤（塞来昔布）和前列腺癌（非那雄胺）。然而,化学预防广泛应用于临床还不现实。分子靶标的深入研究将扩展化学预防的范围并使其个性化。