Biomedical subjects

N Kariv

Publications and source records attributed to N Kariv.

At least 19 recordsLinked to original sources

PubMed2001

Generation of auto-antibodies towards Alzheimer's disease vaccination.

We developed a novel procedure to evoke anti-aggregating beta-amyloid (Abeta) antibodies, using filamentous phages displaying only four amino acids EFRH of the beta-amyloid peptide (AbetaP). This epitope was found to be the main regulatory site for fibril formation. For the first time, effective auto-antibodies have been obtained in guinea-pigs, which exhibit human identity in the AbetaP. Immunization through a phage-carrying epitope was found to be long-lasting, and no toxic effect caused by autoimmune response was detected in the challenged animal sections. These antibodies performed similarly to site-directed monoclonal antibodies and to antibodies raised against fibrillar Abeta in disaggregation of plaques, and may serve as the basis for developing an anti-Abeta vaccine.

Alzheimer Disease↗

PubMed2001

Comparative effects of indomethacin on cell proliferation and cell cycle progression in tumor cells grown in vitro and in vivo.

Considerable research effort is currently being directed towards understanding the mechanisms mediating the antiproliferative effects of non-steroidal anti-inflammatory drugs (NSAIDs) and, more recently, of cyclooxygenase (COX)-2 inhibitors as well. A key question is whether NSAIDs (excluding sulindac) exert their anticarcinogenic effects in vivo by a mechanism that is dependent on their capacity to inhibit COX activity. Some studies with cultured tumor cells in vitro have argued against such a linkage, showing that NSAIDs inhibit cell replication and/or augment apoptosis only at concentrations that exceed those required to inhibit COX activities 10- to 100-fold. The significance of these results for the observed anticarcinogenic effects of NSAIDs in vivo has not yet been evaluated. We addressed this question by comparing, for the same tumor cells, the effects of the NSAID indomethacin on cell growth parameters when the cells were grown in culture to the effects seen in the in vivo growing tumor in the mouse. Indomethacin added to cultured Lewis lung carcinoma cells exerted a potent antiproliferative effect ((3)H thymidine assay) and reduced cell viability (MTT[3-(4,5-dimethyl(thiazol-2-yl)-2,5 diphenyl tetrazolium bromide] assay) at low doses (10-20 microM) in parallel with its inhibitory effect on cellular cyclooxygenase. These effects of indomethacin appeared to arise from a clear antiproliferative shift in the profile of the cell cycle parameters towards a reduced percentage of cells at the S and G(2)/M phases, together with an increased percentage of cells at the G(1) phase. Significantly, similar results were seen when indomethacin was given in vivo at the low dose of 2 mg per kg/day, which blocked blood platelet COX activity and at the same time produced a delay in tumor growth initiation and attenuation of apparent primary tumor growth as well as growth of lung metastases. These results thus provide strong support for the notion that COX inhibition is a major determinant in the antitumorigenic effect of indomethacin in vivo.

Analysis of Variance↗

PubMed2001

Laser soldering of rat skin, using fiberoptic temperature controlled system.

BACKGROUND AND OBJECTIVE: Laser soldering of tissues is based on the application of a biological solder on the approximated edges of a cut. Our goal was to use laser soldering for sealing cuts in skin under temperature feedback control and compare the results with ones obtained using standard sutures. STUDY DESIGN/MATERIALS AND METHODS: Albumin solder was applied onto the approximated edges of cuts created in rat skin. A fiberoptic system was used to deliver the radiation of a CO(2) laser, to heat a spot near the cut edges, and to control the temperature. Laser soldering was carried out, spot by spot, where the temperature at each spot was kept at 65-70 degrees C for 10 sec. RESULTS: The tensile strength of laser-soldered cuts was measured after 3-28 days postoperatively and was found comparable to that of sutured cuts. Histopathological studies showed no thermal damage and less inflammatory reaction than that caused by standard sutures (P = 0.04). CONCLUSIONS: Temperature controlled laser soldering of cuts in rat skin gave strong bonding. The cosmetic and histological results were very good, in comparison to those of standard sutures.

Albumins↗

PubMed2001

Successful intraperitoneal nutrition in rabbits with short-bowel syndrome.

The efficacy of intraperitoneal alimentation as a means of nutritional support for various degrees of short-bowel syndrome was studied, using the rabbit model. Twenty-eight rabbits were divided into 5 groups. Group I had a sham operation; Groups II, III and IV had 50 %, 75 % and 90 % small-bowel resections (SBR), respectively; Group V had a 90 % SBR with intraperitoneal nutrition. All the rabbits received a regular diet and tap water post-operatively. The rabbits in Group V received intraperitoneal alimentation (IPA) by way of a peritoneal catheter inserted at the time of surgery. The nutrition consisted of 10 % dextrose with 5.5 % amino acids. This provided 30 - 35 kcal/kg of additional energy per day. All the rabbits within Group IV (90 % resection without IP nutrition) died within 2 to 5 weeks. IP nutrition enabled body weight to be maintained and prevented the death of all rabbits with 90 % small-bowel resection.

Animals↗

PubMed2001

Carbon dioxide laser and silver halide infrared transmitting fibers for tympanoplasty: an experimental animal model.

OBJECTIVE: This study evaluates the effectiveness and safety of fiberoptic carbon dioxide (CO2) laser welding for graft closure of tympanic membrane perforations in an animal model. STUDY DESIGN AND SETTING: Tympanic membrane perforation was surgically induced in 11 eardrums of 7 given pigs. A lumbar facial graft was placed over the wound, and albumin drops served as a biologic solder. CO2 laser energy, transmitted through silver halide infrared transmitting fibers, was used for "spot-welding" along the circumference of the graft. The welded sites were evaluated by using a surgical microscope as well as by evaluating the sites histologically. RESULTS: Healing started 3 to 4 days after surgery and was completed within 3 weeks with the formation of a neotympanum. Some inflammation with granulation tissue was noted in 5 eardrums. CONCLUSIONS AND SIGNIFICANCE: These preliminary results indicate that CO2 laser tympanoplasty with a fiberoptic delivery system may be a promising new technique for the clinical setting.

Animals↗

PubMed2000

Temperature controlled CO(2) laser welding of soft tissues: urinary bladder welding in different animal models (rats, rabbits, and cats).

BACKGROUND AND OBJECTIVE: Laser welding of tissues is a method of closure of surgical incisions that, in principle, may have advantages over conventional closure methods. It is a noncontact technique that introduces no foreign body, the closure is continuous and watertight, and the procedure is faster and requires less skill to master. However, in practice, there have been difficulties in obtaining strong and reliable welding. We assumed that the quality of the weld depends on the ability to monitor and control the surface temperature of the welded zone during the procedure. Our objective was to develop a "smart" fiberoptic laser system for controlled temperature welding. STUDY DESIGN/MATERIALS AND METHODS: We have developed a welding system based on a CO(2) laser and on infrared transmitting AgClBr fibers. This fiberoptic system plays a double role: transmitting laser power for tissue heating and noncontact (radiometric) temperature monitoring and control. The "true" temperature of the heated tissue was determined by using an improved calibration method. We carried out long-studies of CO(2) laser welding of urinary bladders in various animal models. Cystotomies were performed on the animals, and complete closure of the bladder was obtained with a surface temperature of 55 +/- 5 degrees C at the welding site. RESULTS: In early experiments on 31 rats, the success rate was 73%. In later experiments with 10 rabbits and 3 cats, there was an 80% and a 100% success rate, respectively. CONCLUSION: The success rate in these preliminary experiments and the quality of the weld, as determined histologically, demonstrate that temperature controlled CO(2) laser welding can produce effective welding of tissues. The fiberoptic system can be adapted for endoscopic laser welding.

Animals↗

PubMed2000

Experimental intrauterine growth retardation alters renal development.

Vascular placental insufficiency is considered a common pathogenic factor in human intrauterine growth retardation (IUGR), resulting in small-for-gestational-age, asymmetric newborns. IUGR neonates experience higher morbidity and mortality rates, as well as a possible contribution towards late sequelae, such as hypertension, and cardiovascular disease in adulthood. To simulate vascular placental insufficiency, an experimental rabbit IUGR model was used. Intrauterine growth retardation was achieved by ligation of 25-30% uteroplacental vessels of half of the fetuses during the last third of gestation. Ischemic fetuses were significantly small, asymmetric, and had a disproportionately small body with a relatively large head. The kidneys from all groups were analyzed for relative estimated glomeruli number (REGN) using an unbiased blind design. The glomeruli number was significantly reduced in the asymmetric IUGR rabbit fetuses, probably due to decreased renal vascular supply. Our results support the concept that the reduced number of glomeruli may contribute to impaired renal function, thus predisposing to neonatal renal dysfunction and late sequelae, such as adult hypertension. This study emphasizes the clinical importance of early IUGR diagnosis and prevention.

Animals↗

PubMed1999

Bladder welding in rats using controlled temperature CO2 laser system.

PURPOSE: Laser tissue welding has potential advantages over conventional suture closure of surgical wounds. It is a noncontact technique that introduces no foreign body and limits the possibility of infections and complications. The closure could be immediately watertight and the procedure may be less traumatic, faster and easier. In spite of these positives laser welding has not yet been approved for wide use. The problem in the clinical implementation of this technique arises from the difficulty in defining the conditions under which a highly reliable weld is formed. We have assumed that the successful welding of tissues depends on the ability to monitor and control the surface temperature during the procedure, thereby avoiding underheating or overheating. The purpose of this work was to develop a laser system for reliable welding of urinary tract tissues under good temperature control. MATERIALS AND METHODS: We have developed a "smart" laser system that is capable of a dual role: transmitting CO2 laser power for tissue heating, and noncontact (radiometric) temperature monitoring and control. Bladder opening (cystotomy) was performed in 38 rats. Thirty-three animals underwent laser welding. In 5 rats (control group) the bladder wound was closed with one layer of continuous 6-0 dexon sutures. Reliable welding was obtained when the surface temperature was kept at 71 + 5C. Quality of weld was controlled immediately after operation. The rats were sacrificed on days 2, 10 and 30 for histological study. RESULTS: Bladder closure using the laser welding system was successful in 31/33 (94%) animals. Histological examination revealed an excellent welding and healing of the tissue. CONCLUSIONS: Efficiency of laser welding of urinary bladder in rats was confirmed by high survival rate and quality of scar that was demonstrated by clinical and histological examinations. In the future, optimal laser welding conditions will be studied in larger animals, using CO2 lasers and other lasers, with deeper radiation penetration into tissues.

Animals↗

PubMed1999

Acute iron intoxication: the efficacy of deferiprone and sodium biocarbonate in the prevention of iron absorption from the digestive tract.

To determine whether enteral deferiprone given after a loading dose of liquid iron interferes with iron absorption from the digestive tract, prospective randomized animal study was initiated using Sprague-Dawley rats. The rats were given 20 mg elemental iron/kg as a ferrous sulfate solution + 1 mEq sodium bicarbonate/kg, and then dosed orally with 150 mg deferiprone/kg immediately or after 15 min. Serum iron levels were measured at 1, 3, 5 and 24 h; feces were collected for 24 h. The 20 mg elemental iron/kg caused a significant and rapid increase in serum iron levels to > 350 micrograms/dL within 20 min of oral dosing. Deferiprone, if given immediately after the iron, produced a significant decrease in serum iron levels and a 2-fold increase in iron excretion in feces. Effectiveness was delayed when the deferiprone was given 15 min after the iron dosing. Enteral deferiprone might be useful in preventing cases of acute iron intoxication.

Animals↗

PubMed1998

Chemopreventive effect of aspirin on growth of aberrant crypt foci in rats.

Nonsteroidal anti-inflammatory drugs display a chemopreventive effect on polyps and cancer of the large bowel. This study evaluated the inhibitory effect of aspirin on the distribution and growth of aberrant crypt foci (ACF), the earliest putative preneoplastic and early neoplastic lesions in a rat model. For initiation of ACF, Sprague Dawley rats were injected with azoxymethane (30 mg/kg), a well-established rat carcinogen. After the second injection the rats were allocated to three groups, which received 0.2% or 0.6% aspirin or the solvent only (control group). After 6 weeks the animals were killed, and their colons removed, fixed in formalin, and screened for distribution and size of ACF, separately for middle and distal parts of the large intestine. The rats injected with azoxymethane showed a 100% incidence of ACF. Administration of 0.2% and 0.6% aspirin resulted in 55% and 54% reduction, respectively, in overall frequency of ACF. Aspirin significantly reduced the frequency of medium-sized (four to six crypts per focus) and large (three to six crypts per focus) but not the small (one to three crypts per focus) ACF. In the control group the ACF of the same multiplicity were larger than those in the aspirin-treated rats. No statistically significant difference in ACF-inhibiting effect was noted between 0.6% and 0.2% aspirin solution. Aspirin given at a concentration of either 0.2% of 0.6% thus has a chemopreventive effect on ACF, acting on postinitiation stage of azoxymethane-induced colonic carcinogenesis model in rats.

Animals↗

PubMed1998

Castration prevents calcium channel blocker-induced gingival hyperplasia in beagle dogs.

1. The purpose of this study was to investigate testosterone's role on the calcium channel antagonist oxodipine-inducing gingival hyperplasia in a dog model. 2. Two experiments were conducted using castrated and intact male dogs. Oxodipine was administered orally for 90 days, at a dose of 24 mg/kg/day. In the first experiment, the occurrence of gingival hyperplasia was evaluated. In the second, the gingival index (GI) and gingival hyperplasia index (GHI) were recorded and correlated with serum levels of testosterone. 3. A significant positive correlation between GI, GHI and plasma testosterone was noted. Castrated dogs were injected with testosterone, 4 months after the start of oxodipine treatment, while in the non-castrated dogs, administration of oxodipine was stopped. Castration correlated with lack of GH, while testosterone injection to the same dogs was associated with an increase of GI and GHI. 4. Since it is known that testosterone receptors are present in the gingiva, it is proposed that oxodipine-induced gingival hyperplasia could be mediated by the calcium channel blocker on plasma testosterone levels.

Animals↗

PubMed1993

Leukergy--a new diagnostic test for bone infection.

This new blood test for infection is based on the phenomenon of leukergy in which white cells agglomerate in the peripheral blood of patients with inflammatory diseases. It was used in 26 patients with proven bone or joint infection and was positive in 25. The leukergy test was more accurate than the ESR, white cell count or blood culture. The percentage of cells agglomerated correlated with the clinical severity of the infection and the test detected reactivation of the septic process better than the other haematological tests. It is a rapid and inexpensive method which is useful in the diagnosis and management of bone and joint infections.

Adult↗

PubMed1991

Alteration of macrophage activity in experimental septic shock in the rabbit.

We studied alteration in macrophage activity during experimental septic shock and the effect of the protease inhibitor Trasylol on these alterations. Studies were carried out on three groups of 6 rabbits of each. One group (A) served as a control and in the other two groups (B,C) septic shock was induced using the cecal ligation technique. Group B received i.v. Trasylol prior to and following cecal ligation. The clearance and reticuloendothelial system (R.E.S.) distribution of 125I labelled polyvinyl pyrrolidone (PVP) was used to study macrophage function. PVP was injected into all animals 18 h prior to cecal ligation. For 48 h following the operation, PVP blood levels were repeatedly measured and clearance calculated. The animals were then sacrificed, and total radioactivity of the various organs was measured. In the early stages after cecal ligation a significantly higher PVP clearance rate was noted in groups B and C (P less than 0.01); In the later stages of the experiment, however, group C demonstrated the slowest clearance rate with intermediate values in group B. The highest PVP concentrations were found in the liver and spleen. A significantly higher PVP concentration was noted in the spleen of the animals in group A and B as compared to group C (P less than 0.01) while the difference between group A and B was not significant. Our results indicate that septic shock reduces macrophage function as measured by the changes in PVP clearance and distribution. Injections of Trasylol seem to ameliorate these changes. The model of 125I PVP clearance seems to offer a convenient, valid and informative model for measurement of macrophage activity in pathological conditions.

Animals↗

PubMed1990

Captopril, but not diltiazem, favorably affects the course of early chronic renal disease in rats.

The concepts that increased intracellular Ca2+ content and increased glomerular capillary pressure play an important role in the progression of chronic renal diseases has led to the suggestion that treatment with calcium-blocking agents (diltiazem; CBB) or converting enzyme inhibitors (captopril; CEI) may be indicated to prevent renal failure. We studied the effects of CCB and CEI on the early course of adriamycin (ADR) nephropathy, where glomerular pressure has been shown to be unchanged, blood pressure was only mildly elevated and renal failure incipient. Animals were studied 2, 7, 12, 16 and 20 weeks after the second injection of ADR, 2 mg/kg. In treated rats, blood pressure remained normal. At the end of the study, proteinuria and serum creatine were lower in ADR-CEI than in ADR rats (149 +/- 42 vs. 616 +/- 90 mg/day, p less than 0.01 and 0.36 +/- 0.04 vs. 0.58 +/- 0.02 mg%, p less than 0.01, respectively). ADR-CCB had values similar to those of untreated ADR rats. Mesangial expansion and focal glomerulosclerosis were present only in ADR and ADR-CCB rats, whereas in ADR-CEI rats the glomeruli were virtually normal. Glomerular 45Ca uptake was increased in ADR, decreased in ADR-CCB rats, and normal in ADR-CEI. Glomerular 6-keto PGF1 alpha and TxB2 were significantly increased in ADR rats, and both treatments decreased TxB2. The results suggest that endogenous angiotensin II is important for the early progression of glomerular injury toward renal insufficiency, while tissue Ca2+ accumulation may play an important role in more advanced phases.

Animals↗

PubMed1989

Effects of sodium depletion on renal prostanoid synthesis in rats: influence of the converting enzyme inhibitor captopril.

1. The synthesis of prostaglandin (PG) E2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane (TX) B2 by isolated glomeruli, cortical tubules, inner medullary slices and outer medullary slices was measured in salt-depleted (LNa) rats and in salt-depleted rats receiving captopril (LNa-CEI). Animals were studied before and after 4, 9 and 15 days of Na+ depletion. 2. Na+ balance was reached in LNa rats after 4 days. Blood pressure and creatinine clearance remained stable. Serum Na+ decreased from 140 +/- 1 to 126 +/- 1 mmol/l (mean +/- SEM, P less than 0.01). In contrast, LNa-CEI rats were unable to conserve Na+ adequately: fractional excretion of Na+ and natriuresis were constantly greater than in LNa animals. As a consequence, LNa-CEI rats developed severe hyponatraemia, lost weight and their creatinine clearance decreased. 3. The glomerular synthesis of PGE2, PGF2 alpha and 6-keto-PGF1 alpha, but not of TXB2, was significantly increased in LNa rats. In LNa-CEI rats, the synthesis of PGE2 and 6-keto-PGF1 alpha was similar to control values, but PGF2 alpha and TXB2 synthesis was elevated at day 9. In cortical tubules, PGE2 and PGF2 alpha were unaffected by Na+ depletion, but 6-keto-PGF1 alpha and TXB2 were increased and a similar trend was observed in LNa-CEI rats. In outer medulla of LNa rats, a decrease in all the eicosanoids measured was observed at day 4. In LNa-CEI animals, the synthesis of PGE2 and PGF2 alpha, but not of 6-keto-PGF1 alpha and TXB2, was significantly depressed. In inner medulla, Na+ depletion only tended to decrease PGF2 alpha and 6-keto-PGF1 alpha, but in the presence of captopril, the synthesis of all prostanoids was significantly decreased.

6-Ketoprostaglandin F1 alpha↗

PubMed1989

Changes in renal prostanoid synthesis induced by potassium loading in rats.

Previous works have demonstrated changes in the urinary excretion of prostaglandins (PG) in response to changes in potassium (K) or sodium (Na) intake. In the present study, the production of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and thromboxane B2 (TXB2) by isolated glomeruli, cortical homogenates, medullary and papillary slices was measured in K-loaded rats on either a normal or a low Na intake. In glomeruli, K loading increased selectively PGE2 synthesis. In Na-depleted animals, all prostanoids were elevated and K loading did not induce a further increase. In cortical and medullary preparations, PGE2 was decreased by K loading irrespective of the state of Na balance. In papilla, PGE2 decreased (in all K-loaded rats) and PGF2 alpha increased (only in rats with normal Na intake). 6-Keto-PGF1 alpha and TXB2 did not change significantly. No correlation was present between changes of PG synthesis and urinary kallikrein excretion. The results demonstrate a specific effect of K on PGE2 and PGF2 alpha, and suggest a role for these substances in K homeOstasis.

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Leukergy in inflammatory bowel disease.

In the phenomenon of leukergy, white blood cells agglomerate in peripheral blood slides. This agglomeration has been described in inflammatory infections of various causes. This study assesses this phenomenon in inflammatory bowel disease. A correlation was found between the severity of inflammatory bowel disease activity and the percentage of leukergy. Leukergy was found to parallel the clinical and endoscopic findings of inflammatory bowel disease. Furthermore, leukergy was found to be more accurate than white blood count and erythrocyte sedimentation rate. It is also found to accurately assess the course of the disease when clinical and other laboratory tests were masked by steroid and antibiotic administrations. Leukergy is a quick, inexpensive test that can easily be performed at the patient's bedside.

Adolescent↗

PubMed1988

Enhanced electroretinogram in cats induced by exposure to mercury acetate.

The present study was undertaken in order to verify whether, and how, retinal functions are affected by subacute poisoning with organic mercury. Mercury acetate in various concentrations (0.025-0.25 mg/kg per day) was injected subcutaneously every second day to adult cats (N = 20) throughout a 2.5-4.0-week period. The electroretinogram (ERG) was recorded and the Hg2+ concentrations in the blood were determined. In nearly 90% of the intoxicated cats an enhanced electroretinogram (scotopic b-wave amplitude) was found as compared to its level in the normal control cats (N = 10). The latency of the ERG was found to be appropriately shorter, up to a maximal difference of nearly 20% in comparison to the controls. Hg2+ was present in the blood of the exposed cats during a 2.5-month period following the exposure. It is concluded that exposure to mercury acetate induces a permanent increase in the excitability level of the cat's retina.

Animals↗