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Biomedical subjects

J Shani

Publications and source records attributed to J Shani.

At least 37 records · Page 2Linked to original sources

Woven bone formation around implants and the effect of bacterial infection.

Several implant materials used in dental and orthopedic surgery were placed in rat tibial bones to study their effects on mineralization. The implants consisted of bone bonding and non-bonding materials. Changes in mineralization were defined by morphometric analysis of matrix vesicle distribution at the implant interface and in normal bone healing following marrow injury. Bone-bonding materials induced an increase in matrix vesicle activity. This finding was supported by study of the biochemical changes in the same model that manifested high correlations to the morphometrical observations with regard to enhancement or delay of primary mineralization. In addition, the study of healing using nuclear methods indicated that implants alter bone healing as shown by the different uptakes of 99mTc and 32P in the different bone compartments. Decreased 32P uptake by the organic phase in the presence of bone-bonding implants suggested that cleavage of 99mTc-MD32P into its technetium and methylene diphosphonate moieties was inhibited by administration of implants. Further studies on the effect of bacterial infection on the peri-implant tissues revealed a decrease in woven bone formation due to infection.

Animals↗

Final results of the Balloon vs Optimal Atherectomy Trial (BOAT)

BACKGROUND: Previous directional coronary atherectomy (DCA) trials have shown no significant reduction in angiographic restenosis, more in-hospital complications, and higher 1-year mortality than conventional balloon angioplasty (percutaneous transluminal coronary angioplasty [PTCA]). DCA, however, has subsequently evolved toward a more "optimal" technique (larger devices, more extensive tissue removal, and routine postdilation to obtain diameter stenosis <20%). METHODS AND RESULTS: The Balloon vs Optimal Atherectomy Trial (BOAT) was conducted to evaluate whether optimal DCA provides short- and long-term benefits compared with balloon angioplasty. One thousand patients with single de novo, native vessel lesions were randomized to either DCA or PTCA at 37 participating centers. Lesion success was obtained in 99% versus 97% (P=.02) of patients to a final residual diameter stenosis of 15% versus 28% (P<.0001) for DCA and PTCA, respectively, the latter including stents in 9.3% of the patients. There was no increase in major complications (death, Q-wave myocardial infarction, or emergent coronary artery bypass graft surgery [2.8% versus 3.3%]), although creatine kinase-MB >3X normal was more common with DCA (16% versus 6%; P<.0001). Angiographic restudy (in 79.6% of eligible patients at 7.2+/-2.6 [median, 6.9] months) showed a significant reduction in the prespecified primary end point of angiographic restenosis by DCA (31.4% versus 39.8%; P=.016). Clinical follow-up to 1 year showed nonsignificant 13% to 17% reductions in the DCA arm of the study for mortality rate (0.6% versus 1.6%; P=.14), target-vessel revascularization (17.1% versus 19.7%; P=.33), target-site revascularization (15.3% versus 18.3%; P=.23), and target-vessel failure (death, Q-wave myocardial infarction, or target-vessel revascularization, 21.1% versus 24.8%; P=.17). CONCLUSIONS: Optimal DCA provides significantly higher short-term success, lower residual stenosis, and lower angiographic restenosis than conventional PTCA, despite failing to reach statistical significance for reducing late clinical events compared with PTCA with stent backup.

Aged↗

Safety of solar phototherapy at the Dead Sea.

BACKGROUND: Climatotherapy at the Dead Sea is effective for patients with psoriasis, atopic dermatitis, vitiligo, and other diseases. Although impressive improvement has been reported for patients with psoriasis, with a clearance rate of more than 80% after a 4-week stay, questions regarding the safety of this treatment have arisen. OBJECTIVE AND METHODS: We compare the mean UVB radiation intensities absorbed by psoriatic patients undergoing a 4-week climatotherapy under supervision at the DMZ Rehabilitation Clinic of Ein-Bokek (The Dead Sea, Israel), with similar climatotherapy studies in Sweden and Switzerland. We also compare the climatotherapy radiation dosages with the UVB intensities absorbed by psoriatic patients in radiation cabins at seven university clinics. RESULTS: According to our individually computerized DMZ protocol, a psoriasis patient with skin type IV is exposed during a 4-week climatotherapy to a mean 3.11 J/cm2 (148 MED) of UVB, similar to that in Sweden and Switzerland. The range of the in-clinic annual phototherapy in the seven medical centers studied varied from 1.17 to 37.80 J/cm2 (56 to 1800 MED). CONCLUSION: When all relevant factors are taken into account, the mean UVB exposure dose at the Dead Sea is one of the lowest reported for clearance of psoriatic plaques.

Humans↗

Effect of desipramine on immunological parameters in mice, and their reversal by stress.

Immunomodulation of cell-mediated immunity is demonstrated in mice, after administration of desipramine, a noradrenaline-reuptake inhibitor, with or without exposing the mice later to an acute swimming stress. A single i.p. injection of 10 mg/kg desipramine to naive mice increased the relative weight of their spleens, the response of their splenocytes to the mitogen concavaline-A and their ability to produce IL-10, as compared to saline controls. Exposing the desipramine-treated mice to a swimming stress significantly reduced these parameters, as well as the levels of IL-2 and IFN-gamma, as compared to desipramine-treated mice. Stress alone reduced the weight of the spleen, and the ability of splenocytes to produce IFN-gamma. As desipramine and acute stress have stimulatory effect on the sympathetic system, it is suggested that a concomitant administration of the drug and a stressful event of these mice, change the splenocytes' micro-environment of sympathetic transmitters, and inhibit their function. These results may be partially due to impairment in the T-helper cell function by a beta-adrenoreceptor-dependent mechanism.

Animals↗

Magnesium in the management of asthma: critical review of acute and chronic treatments, and Deutsches Medizinisches Zentrum's (DMZ's) clinical experience at the Dead Sea.

The recognition of asthma as an inflammatory disease has led over the past 20 years to a major shift in its pharmacotherapy. The previous emphasis on using relatively short-acting agents for relieving bronchospasms and for removing bronchial mucus has shifted toward long-term strategies with the use of inhaled corticosteroids, which successfully prevent and abolish airway inflammation. Because some of the biological, chemical, and immunological processes that characterize asthma also underly arthritis and other inflammatory diseases, and because many of these conditions have been successfully treated for the past 40 years at the Dead Sea, we were not surprised to realize and record the significant improvement of asthmatic condition after a 4-week stay at the Dead Sea: lung function was improved, the number and severity of attacks was reduced, and the efficacy of beta2-agonist treatments was improved. After reviewing the acute and chronic treatments of asthma in the clinic (including emergency rooms) with magnesium compounds, and the use of such salts as supplementary agents in respiratory diseases, we suggest that the improvement in the asthmatic condition at the Dead Sea may be due to absorption of this element through the skin and via the lungs, and due to its involvement in anti-inflammatory and vasodilatatory processes.

Ambulatory Care Facilities↗

Effect of sciatic denervation on cell-mediated immunity.

Local semiallogenic graft-versus-host (GvH) and host-versus-graft (HvG) reactions were induced in mice whose right hind limbs had been partially denervated surgically. The denervation was performed by removing a 2 mm segment of the sciatic nerve, while sham-operated and non-operated mice served as controls. Eight days after denervation the mice were injected with spleen cells from a 3-month-old C57BL female, or from (C57xCBA)F1 male mice, and the GvH and HvG reactions were evaluated, 7 or 10 days later, by quantitatively estimating the weight (enlargement) of the popliteal lymph-nodes. Significant weight increases of 51% (for the GvH reaction) and 63% (for the HvG reaction) were observed in the denervated mice, when compared to the sham-operated ones. This increased cell-type reactivity in a denervated limbs seems to be related to the immunostimulatory activity of cytokines which are released by cells engaged in repair processes of damaged nerves, as well as related to the reduction of the immunosuppressive effect of noradrenergic innervation in the denervated animals.

Adoptive Transfer↗

Demographic evaluation of successful antipsoriatic climatotherapy at the Dead Sea (Israel) DMZ Clinic.

BACKGROUND: Natural balneologic properties, thermomineral springs and unequivocal success in improving psoriasis, attract an ever-growing number of psoriatics to the DMZ Clinic on the shores of the Dead Sea in Israel. METHODS: This paper analyses the rate of success of this balneotherapy in 740 psoriatics who flew in from Germany specifically for this treatment, during 1995, as a function of sex, family history of the disease, number of previous treatments at the Dead Sea, skin type, skin involvement, joint involvement, duration of treatment, sun-exposure schedule, remission length, and psychologic supervision. RESULTS: After 4 weeks, 70% of the patients were completely cleared, this improvement being about the same across both sexes. Family history of the disease, skin type, and psychologic support did not affect the rate of success. On the other hand, previous treatments at the Dead Sea, moderate to severe skin surface involvement, and participation of arthritis, improved the chance of better clearing of the psoriatic condition. Similar improvement was obtained by a longer sun-exposure schedule and a complete-4-week treatment. CONCLUSION: These results indicate that the medical improvement in the psoriatic condition after a 4-week stay at the Dead Sea can be better enhanced and its remission prolonged if additional demographic and anamnestic factors are carefully taken into account.

Adolescent↗

Effect of hypothalamic lesion or chemical axotomy on restitution of immunoreactivity in mice after cyclophosphamide administration.

Splenocytes harvested from mice that underwent chemical axotomy (by 6-hydroxydopamine) or that had electric lesions in their anterior hypothalami demonstrated a significant decrease in their proliferative ability after concanavalin-A stimulation in vitro. In axotomized mice pre-treated with cyclophosphamide, faster restitution of the proliferative activity was observed on days 6-8 after the drug's administration. Splenocytes isolated from mice treated with 6-hydroxydopamine did not exhibit any suppressive activity, which is characteristic of the restitution period following administration of cyclophosphamide. These results indicate that the autonomic nervous system exert a direct effect on immunoreactivity and on processes which are responsible for restitution after cyclophosphamide-induced immunodisorders.

Animals↗

Inhibition of neutrophils' chemiluminescence by ethanol extract of propolis (EEP) and its phenolic components.

Ethanol extract of propolis (EEP), a natural beehive product, has been known for centuries for a variety of beneficial traditional medical properties, among which an anti-inflammatory effect is a major one. Now that most of its components have been isolated and recently identified, we tested 19 of them (all phenolic compounds) for their degree of anti-inflammatory activity. This was performed by evaluating the luminol-enhanced chemiluminescence, formed after their scavenging free radicals, generated by neutrophils that had been stimulated by phorbol myristate acetate. Caffeic-acid-phenylethyl-ester abolished the chemiluminescence completely at a concentration of 10 microM, while three flavone derivatives and three flavonols (galangin, kaempferol and kaempferid) diminished this chemiluminescence by 73-93% at the same concentration. These results indicate that some of the phenolic components of the ethanol extract of propolis are its active components in exerting its renowned anti-inflammatory activity.

Animals↗

Failure to detect Chlamydia pneumoniae in coronary atheromas of patients undergoing atherectomy.

To further investigate a proposed relationship between Chlamydia pneumoniae and coronary heart disease, coronary atheromas were collected from patients undergoing percutaneous atherectomy. Fifty-eight atheroma specimens were examined by culture and polymerase chain reaction (PCR) and 22 by electron microscopy. All were negative for C. pneumoniae, except a single specimen that was PCR-positive. These results differ from studies in other populations, in which this organism was identified by nonculture methods within coronary atheromas obtained at autopsy. Anti-C. pneumoniae antibody titers from 65 of the patients were compared with those of 28 asymptomatic controls. IgG titers were higher in controls than in patients. There is no evidence that C. pneumoniae exists within atheromas in this study population, nor does seroprevalence correlate with the presence of coronary disease in these patients.

Adult↗

A quantitative morphometric study of the kinetics of tissue regeneration after administration of cisplatin.

The effect of the anti-neoplastic drug cisplatin was investigated on several rat tissues using a novel computerized morphometric image analysis system. The rats were sacrificed in pre-determined intervals, ranging from 1 to 36 days after drug administration, and their liver, kidneys and external ears were sampled and sectioned. Tritiated thymidine was injected into each rat 1 h prior to sacrifice to enable autoradiographical explorations. All sections were histomorphometrically studied by a computerized system. The kidneys of the experimental group revealed increased tubular diameters, especially in the corticomedular region. In the ears, decreases of the mean epithelial thickness, in the mean number of nuclei and in the mean nuclear surface were observed. The thickness of the connective tissue also decreased significantly by the end of the first week and returned to its normal size later on. No changes were detected in the ear cartilage. In the liver, no morphometrical differences were noticed in the hepatocyte density, Kupffer cell density or nuclear area. The nuclei of the hepatocytes and Kupffer cells retained a constant ratio to the total number of cells throughout the whole experiment. Liver autoradiography revealed that the hepatocyte and Kupffer cell labelling indexes after cisplatin administration were significantly higher than those of the control group, indicating enhanced replication of cells and increased synthesis of DNA, which in turn is accumulated in the nuclei and turn the cells into polyploids. In addition, the mean radius of the liver acini after cisplatin was diminished, followed by a significant reduction in the size of the progenitor compartment. It is concluded that while the kidneys are the organs most affected by cisplatin, the progenitor compartment of the liver is heavily affected as well. Computerized morphometry was demonstrated as a highly reproducible and accurate quantitative method for evaluation of histopathological changes in various mammalian tissues.

Animals↗

Inhibition of proliferation of psoriatic and healthy fibroblasts in cell culture by selected Dead-sea salts.

The effect of five selected minerals abundant in the Dead-sea brine was studied on proliferation of fibroblasts grown from psoriatic and healthy skin biopsy specimens in cell culture. The reason for carrying out this study was looking for the mechanism of the antiproliferative effect of selective Dead-sea minerals in improving the psoriatic condition. Psoriatic skin shave biopsy specimens (both from involved and uninvolved areas of the body) as well as healthy skin (obtained from amputated limbs) were incubated in tissue culture, and their outgrowing fibroblasts were used for this study. The number of cells and their cyclic AMP content were used as parameters for cell division and for proving the selective involvement of magnesium salts in the antiproliferative effect. It is shown that the inhibitory effects of magnesium bromide and magnesium chloride on cell growth were significantly stronger than those of their corresponding potassium salts or of sodium chloride. These results were obtained with both psoriatic and healthy skin fibroblasts, indicating that the inhibitory effect of the selected Dead-sea minerals is present in healthy and psoriatic skin cells.

Baths↗

Cytomegalovirus replication is not a cause of instability in unstable angina.

BACKGROUND: Unstable angina is most frequently caused by coronary thrombosis, with or without plaque fissure, but the mechanisms underlying these events are still speculative. Since cytomegalovirus (CMV) antigens and DNA encoding CMV major immediate-early (MIE) gene have been detected in atherosclerotic arterial walls, the active replication of CMV may be responsible for plaque instability. Therefore the expression of CMV MIE gene mRNA, an early marker of viral replication, was assessed in coronary atherectomy specimens from patients with stable or unstable angina. METHODS AND RESULTS: Twenty patients with unstable angina (12 men and 8 women; mean age, 62 years; range, 44 to 89 years) and 20 patients with stable angina (16 men and 4 women; mean age, 62 years; range, 43 to 81 years) who underwent successful directional coronary atherectomy were enrolled in the study. The efficiency of mRNA extraction, transcription, and amplification from each coronary atherectomy specimen was assessed by performance of reverse transcription and thermal cycling amplification of a 548-bp human beta-actin cDNA segment. After Southern blotting and hybridization with a specific probe, all specimens but one showed a positive hybridization signal. The negative sample was excluded from the study. Reverse transcription and thermal cycling amplification of a 145-bp CMV cDNA segment of the MIE gene were then carried out. After Southern blotting and hybridization with a specific probe, none of the specimens showed a positive hybridization signal. Plasmid pACYC 184 containing the Xba I-inserted MIE gene cDNA was used as a positive control: as few as 10 molecules of the plasmid per reaction were detectable after amplification. CONCLUSIONS: Our results do not support the hypothesis that, in patients with unstable angina, replication of CMV in coronary atherosclerotic plaques is a major cause of plaque instability. These findings suggest that the research for the causes of unstable angina should be directed toward processes other than CMV replication.

Angina Pectoris↗

Uptake and biodistribution of 99mtechnetium methylene-[32P] diphosphonate during endosteal healing around titanium, stainless steel and hydroxyapatite implants in rat tibial bone.

Early evaluation of intraosseous implant success and failure is critical, but, until now, there have been no reliable systems of measurement. The present study assessed whether the use of 99mtechnetium methylene-[32P]diphosphonate (99mTcMD32P), a marker for both bone formation and mineralization, can indicate if an implant is bone-bonding or non-bonding. Moreover, this study examined how bone-bonding (titanium and hydroxyapatite) and non-bonding (stainless steel) implants affected the normal healing of bone after marrow ablation, as measured by uptake of 99mTc and 32P. Titanium, hydroxyapatite and stainless steel implants were placed in the right tibiae of Sabra strain rats following ablation of the marrow, and 99mTcMD32P was injected 18 h before harvest. AT 3, 6, 14, 21 and 42 d (and in some experiments, on days 28 and 35) post-injury, the treated and contralateral tibiae were removed and cleaned of soft tissue. The uptake of 99mTc and 32P was measured in the whole bone, as well as in its organic and inorganic phases. Effects of the implants were assessed by comparing the treated to the untreated tibia in each rat. The distribution of 99mTc and 32P varied with each implant. After the insertion of titanium, increased 99mTc uptake was seen in whole bone and in the inorganic and organic phases at days 6-14. 32P uptake in whole bone and in the inorganic phase increased only at day 6, and 32P uptake was decreased in the organic phase at that time. In tibiae implanted with hydroxyapatite, 99mTc and 32P uptake was seen in the whole bone at days 6 and 14. While 99mTc uptake was increased in both the organic and inorganic phases, 32P uptake into the organic phase was decreased at both day 6 and day 14. In tibiae implanted with stainless steel, effects were observed only on day 6. The increased 99mTc uptake in whole bone reflected increases in both the organic and mineral phases. Increased 32P uptake was observed in whole bone as well, due to an increase in the 32P uptake in the mineral phase only; incorporation of 32P in the organic phase was comparable to that found in the contralateral limb. The results of this study indicate that implants alter bone healing, as indicated by the uptake of 99mTc and 32P in the different bone compartments. Moreover, decreased 32P uptake by the organic phase in the presence of bone-bonding implants suggests that cleavage of 99mTcMD32P into its technetium and methylene diphosphonate moieties was inhibited, perhaps as a function of the onset of calcification in the newly synthesized osteoid. The effect of the implants on bone healing was observed on days 6-14, when active bone formation and mineralization were occurring, supporting the hypothesis that these materials events associated with initial calcification. Uptake of 99mTc varies as a function of time, and uptake of 32P varies with time and distribution in the mineral or organic phase of bone, suggesting that these parameters may be useful as indicators of bone-bonding.

Animals↗

Sustained decrease of blood pressure in psoriatic patients during treatment at the Dead Sea.

The diastolic and systolic blood pressure of 1366 psoriatic patients, treated at the Dead Sea for a period of 4 weeks, was monitored from the day following their arrival. The patients were divided into three categories: (a) psoriatics on antihypertensive medication; (b) psoriatics not receiving antihypertensive medication, but whose initial diastolic blood pressure equaled or exceeded 90 mmHg, and (c) psoriatics with normal blood pressure (diastolic pressure lower than 90 mmHg). A paired t-test revealed that the systolic blood pressure of the two hypertensive groups (a and b) dropped by an average of 22 mmHg, and the diastolic blood pressure dropped by 11 and 16 mmHg, respectively. The drop was evident 2 days after their arrival, and leveled off only after 2 weeks. A similar drop in systolic blood pressure was observed in normotensive psoriatics. On the basis of this study it may be concluded that high blood pressure is not a contraindication for the treatment of psoriasis at the Dead Sea.

Adult↗

Modulation of luminol-dependent chemiluminescence of murine macrophages by flavone and its synthetic derivatives.

The effect of flavone (CAS 525-82-6, 2-phenylbenzopyran-4-one, 1), flavone-8-acetic acid (CSA 87626-55-9, FAA, 2) and 10 substituted flavones on the luminol-dependent chemiluminescence of murine macrophages was studied in vitro. The synthetic derivatives were variously substituted with halo, nitro, amino, hydroxy and methoxy substituents in the 3' and 4' positions. Chemiluminescence was used in this study as an indicator for the production of reactive oxygen species by macrophages, stimulated in vitro by phorbol myristate acetate (PMA). All flavones except FAA (2) showed more than 20% inhibition at 10 mumol/l or 100 mumol/l. 3'-Amino-4'-hydroxyflavone (8) was the most potent inhibitor. The IC50s for inhibition of chemiluminescence were 4.2 +/- 1.1 mumol/l, 5.0 +/- 1.0 mumol/l and 3.3 +/- 1.4 mumol/l for resident, elicited and LPS-Poly I:C-primed macrophages, respectively. Small but statistically significant enhancements of chemiluminescence were caused by low concentrations of flavone (1), FAA (2) and 4'-methoxyflavone (6). These results suggest that modulation of the chemiluminescent capacity of macrophages depends on the nature of the substituents and the concentration of the flavones.

Animals↗