Botulinum toxin blocks mast cells and prevents rosacea like inflammation

Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Effects of magnetic resonance imaging diffusion gradient recalled echo on a patient with an intracranial hemorrhage presenting to the emergency department.

Generally, a computed tomography scan is conducted for the diagnosis of stroke in the emergency department, because these scans are easier and faster in the detection of stroke. If there are no signs of hemorrhage on computed tomography scan, an ischemic stroke is diagnosed and treated accordingly. A magnetic resonance imaging scan may be taken in order to verify ischemic stroke. This process may lead to improper treatment and is time consuming. To address this situation, case studies are presented in which magnetic resonance imaging diffusion-weighted imaging and gradient recalled echo were performed to detect hemorrhagic and ischemic stroke and particularly, subarachnoid hemorrhage, which is undetectable with a computed tomography scan.     

Reversal of vascular 18F-FDG uptake with plasma high-density lipoprotein elevation by atherogenic risk reduction

Vascular 18F-FDG uptake marker represents inflammation in atherosclerotic lesions, but whether inflammation can be reversed by risk-modifying interventions has not, to our knowledge, been demonstrated. In this study, we evaluated the change of vascular 18F-FDG uptake in response to lifestyle intervention on serial PET/CT scans and further assessed how the findings relate to atherogenic risk reduction. METHODS: A total of 60 healthy adults underwent 18F-FDG PET/CT scans and atherogenic risk-factor assessment at baseline and again after 17.1 +/- 8.3 mo of practicing lifestyle modification. The PET/CT images were evaluated for the presence of vascular 18F-FDG lesions, and vessel-to-blood-pool 18F-FDG ratios were measured. Indices from summed ratios of positive lesions were compared and correlated to atherogenic risk factors. RESULTS: At follow-up, significant reductions in diastolic blood pressure (P < 0.05), total cholesterol (P < 0.05), and low-density lipoprotein level (P < 0.05) and an increase in high-density lipoprotein (HDL) level (P < 0.0001) were demonstrated. On the initial PET/CT scan, 50 of 60 subjects showed 1 or more 18F-FDG-positive lesions (5.9 +/- 5.0/subject), leading to a total of 352 vascular sites. On follow-up, 18F-FDG-positive lesions were significantly reduced to 2.1 +/- 2.2 sites per subject (P < 0.0001) and a total of 124 sites (64.8% reduction). Follow-up 18F-FDG-positive rates were significantly reduced for the aorta and iliac arteries. In addition, significant reductions in the whole-body 18F-FDG index from 1.39 +/- 1.23 to 0.53 +/- 0.59 (P < 0.0001) and carotid 18F-FDG index from 0.08 +/- 0.16 to 0.03 +/- 0.06 (P = 0.01) were shown. The whole-body 18F-FDG index correlated with total cholesterol (P < 0.05) and HDL level (P < 0.05), and the magnitude of reduction in the 18F-FDG index closely correlated to the amount of increase in plasma HDL level (P = 0.005). CONCLUSION: Our study demonstrated that vascular 18F-FDG uptake is reversed in response to atherogenic risk reduction by lifestyle intervention and that the magnitude of improvement correlates to increases in plasma HDL levels. Thus, serial 18F-FDG PET/CT may be useful for monitoring improvements in the inflammatory component of atherosclerotic lesions in response to risk modification.     

Uncooked rice of relatively low gelatinization degree resulted in lower metabolic glucose and insulin responses compared with cooked rice in female college students

Cooking processes that gelatinize granules or disrupt structure might increase the glucose and insulin responses because a disruption of the structure of starch by gelatinization increases its availability for digestion and absorption in the small intestine. We hypothesized that the uncooked form of rice, which has a relatively low degree of gelatinization even though in powder form, would result in lower metabolic glucose and insulin responses compared with cooked rice (CR). To assess the effects of the gelatinization of rice on metabolic response of glucose and insulin, we investigated the glucose and insulin responses to 3 rice meals of different gelatinization degree in female college students (n = 12): CR (76.9% gelatinized), uncooked rice powder (UP; 3.5% gelatinized), and uncooked freeze-dried rice powder (UFP; 5.4% gelatinized). Uncooked rice powders (UP and UFP) induced lower glucose and insulin responses compared with CR. The relatively low gelatinization degree of UPs resulted in low metabolic responses in terms of the glycemic index (CR: 72.4% vs UP: 49.7%, UFP: 59.8%) and insulin index (CR: 94.8% vs UP: 74.4%, UFP: 68.0%). In summary, UPs that were less gelatinized than CR induced low postprandial glucose and insulin responses.     

Notochordal cells stimulate migration of cartilage end plate chondrocytes of the intervertebral disc in in vitro cell migration assays

Background contextIt was recently demonstrated that the postnatal transition from a notochordal to a fibrocartilaginous nucleus pulposus (NP) is accomplished exogenously by chondrocytes migrating from hyaline cartilage end plates (CEs) into the ectopic notochordal NP region. Although our previous in vivo studies showed evidences for the migration of CE chondrocyte from hyaline CEs into the notochordal NP, it is unknown whether CE chondrocytes of the intervertebral disc (IVD) really have a motile property. In addition, the effect of notochordal cells on this property has not been elucidated.PurposeThe purpose of this in vitro study was to demonstrate whether CE chondrocytes of the IVD are capable of migration, and whether there is any biological link between notochordal cells and CE chondrocytes that may regulate the CE chondrocyte migration.Study design/settingIn vitro cell migration assays were performed using rat IVDs.MethodsNotochordal cells and chondrocytes were obtained from the NP and CE tissues, respectively, and were cultured separately. The different numbers of notochordal cells and the supernatant (conditioned medium) that contained soluble factors produced by notochordal cells were used to demonstrate their effects on the migration of CE chondrocytes. Bovine serum albumin (BSA) and lysophosphatidic acid (LPA) were used as negative and positive controls, respectively.ResultsCompared with BSA, LPA, notochordal cells (N=4×, 2×, 1×, and 0.5×10⁵), and its conditioned media (unconcentrated and fivefold concentrated) significantly increased migration of CE chondrocytes (p<.05 in all comparisons). Particularly, notochordal cells and its conditioned media increased migration in a number- and concentration-dependent manner, respectively.ConclusionsThis study demonstrates that CE chondrocytes of the IVD are capable of migration and that soluble factors produced by notochordal cells stimulate the migration. These results provide a plausible explanation to the question of why CE chondrocytes of the IVD migrate into the ectopic NP region during the natural transition from the notochordal to fibrocartilaginous NP.     

Inhibition of bone healing by pamidronate in calvarial bony defects.

OBJECTIVE: Pamidronate has been studied as a therapeutic drug for various osteopenic diseases. However, avascular osteonecrosis in the jawbone has been recently reported in patients receiving pamidronate. The objective of this study was to examine the effect of pamidronate on bone regeneration in a controlled animal model. MATERIALS AND METHODS: To determine the effect of parmidronate on bone healing in a local bony defect area, a rabbit calvarial bony defect model was used and poly L-lactide-co-glycolide (PLGA) used as a drug carrier material. Four defect groups were made in each rabbit calvaria and the defects were treated as follows: untreated bony defect (group 1), PLGA only (group 2), 2 mg of pamidronate with PLGA (group 3), and 3 mg of pamidronate with PLGA (group 4). Bone healing was evaluated by radiography and histology at 1, 2, 4, 6, and 8 weeks after surgery. RESULTS: In radiographic analysis, radiopacity was lower in pamidronate groups than non-operated rabbit calvarial bone at all observation points (P < .05). In histological analysis, the initial bone formation at 1 week was not different among groups, but it was much lower in the pamidronate groups than in the control or PLGA group after 2 weeks. Newly formed bone at 1 week underwent avascular necrosis after 2 weeks in both pamidronate groups. Avascular necrosis was not observed until 8 weeks in both topically applied pamidronate groups. CONCLUSION: Collectively, pamidronate inhibits bone healing in rabbit calvarial bony defect and it may explain the avascular necrosis of the jaws in patients receiving pamidronate.     

Chiropractic practice in Hong Kong: the need for amendments of health laws and provisions

Chiropractic practitioners with accredited qualifications should have the right to diagnose, the right to operate diagnostic imaging machines, and the right to the title doctor and Yee San. This paper reviews chiropractic practice in Hong Kong as well as laws and provisions of the health professions namely Chiropractors Registration Ordinance, Medical Registration Ordinance, Dentists Registration Ordinance, Radiation Ordinance, and the provisions of codes of practice of Medical Laboratory Technologists and Radiographers. The need for amendments of relevant sections of health laws and provisions, which concern chiropractic rights, chiropractic practice, and clinical research of mechanical neuromusculoskeletal disorders is discussed. Patient privileges relevant to chiropractic practice are proposed. The Chinese title Yee San or Yee and the English title Doctor are generic terms. Hence, legally “Yee San” and “Doctor” should not be coined by medical practitioners and vice versa. Diagnostic imaging and laboratory procedures are essential for differential diagnosis of neuromusculoskeletal disorders, which may indicate or contraindicate the application of manipulation, and hence are essential for chiropractic practice and clinical research. Proposed amendments of the listed sections of the ordinances and provisions are also outlined.     

Somatic gene therapy for phenylketonuria and other hepatic deficiencies

Summary Gene therapy is the delivery of genetic material to specific cell types of an organism to alter its physiology or function. This technology is being explored as a means of treating diseases caused by deficiencies of hepatic gene products. The two diseases being used as models for hepatic gene therapy are classical phenylketonuria (PKU) and haemophilia B. Vectors derived from adenoviruses can be used to completely correct these diseases in animal models. The phenotypic correction generated in these studies is transient, and cannot be duplicated by vector readministration. The transient nature of transgene expression results from the destruction of the virally-transduced cells by a cellular immune response directed against the late viral gene products that are also expressed in the target cells. The inability to repeatedly administer virus is caused by a humoral immune response directed against viral proteins present at the time of infusion. If the host immune response is suppressed, transgene expression can persist for 6 months or more. These findings suggest that host immunomodulation in combination with further modification of the adenoviral vector to reduce or eliminate late viral gene expression may permit long-term expression of potentially therapeutic gene products in mammalian liver.     

Transforming Growth Factor-β1 Induces Apoptosis through Down-Regulation of c-mycGene and Overexpression of p27Protein in Cervical Carcinoma

Transforming growth factor-β1 (TGF-β1) is known to be a potent growth inhibitor for many cell types, including most epithelial cells. In skin keratinocytes, TGF-β1 has been shown to inhibit growth and to rapidly reduce c-mycexpression. However, the molecular mechanism of TGF-β1 action on cell growth of cervical carcinoma has not yet been elucidated. We thus assessed the effect of TGF-β1 on the growth of cervical carcinoma cell lines. Two cervical squamous carcinoma cell lines, CUMC-3 and CUMC-6, were incubated with varying concentrations of TGF-β1, and growth inhibition was evaluated with tetrazolium-based colorimetric assay. After culture in TGF-β1 for 24 h, inhibition of growth was detected in a dose-dependent manner at concentrations of 0.1–10 ng/ml in both cell lines. This effect of TGF-β1 on cultured carcinoma cells was associated with apoptotic process including oligonucleosomal ladder DNA and apoptotic body formations. Northern blot analysis revealed c-mycmRNA expression was suppressed by 10 ng/ml of TGF-β1 following 3 h of treatment in both cell lines. Western blot analysis showed that the level of p27^Kip1protein was increased after TGF-β1 treatment in both cell lines. These results suggest that the mechanisms by which TGF-β1 inhibits the growth of cervical carcinoma are complex and may include effects on down-regulation of c-mycgene, and overexpression of p27^Kip1protein.     

Long-term storage effects on canine osteochondral allografts.

We have studied long-term (to 60 days) effects of 4 degrees C storage in culture media on the histologic, mechanical, and chemical properties of the cartilage from osteochondral shell allografts from the dog. The structural integrity of the cartilage matrix was intact up to 60 days of storage, for the mechanical properties represented by the aggregate modulus and apparent permeability remained normal. These data are supported by normal safranin-O staining as well as normal glycosaminoglycan content and total collagen concentration. However, chondrocyte viability, as assessed by 35SO4 uptake and hematoxylin and eosin preparations, decreased dramatically with time. We believe that the longer storage to 60 days is not indicated, unless conditions can be modified to maintain cell viability.