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PubMed1985

Acute effect of DMBA application on mitotic activity of hamster buccal pouch epithelium.

One, two, or three applications of a 0.5% solution of DMBA in mineral oil were made to the buccal pouches of three groups of hamsters. There were 10 animals in each group, and additional groups of 10 animals were used as mineral oil controls. Mitotic activity was studied in epithelial whole mounts of buccal pouch following intraperitoneal injection of vinblastine (VBL) in a dose of 4 mg per kilogram of body weight 4 1/2 hours, 24 hours, 48 hours, 1 week, and 2 weeks after treatment. Similar groups of animals were used for a thymidine-labeling experiment. Immediately after the last DMBA application to buccal pouches, 3H-TdR was injected intraperitoneally in a dose of 1 microcurie per gram of body weight. All labeling was studied autoradiographically in epithelial whole mounts of buccal pouches stained with hematoxylin. A cell with five or more grains of label per nucleus was considered labeled. It was found that with one application of DMBA mitotic activity, as studied after VBL injection, was greatly reduced during the experimental period of 2 weeks. After two DMBA applications there was a significant reduction in mitotic activity in the first 48 hours but a return to normal by 2 weeks, indicating a reaction to the damage produced by the two DMBA applications. The thymidine-labeling study tended to confirm this result. The label in the animals that received two DMBA applications disappeared after 48 hours, indicating increased mitotic activity and tissue repair, while animals with one DMBA application maintained the label after 1 week.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

S-allylcysteine ameliorates doxorubicin toxicity in the heart and liver in mice.

Doxorubicin, a potent anticancer drug, is effective against a wide range of human neoplasms. However, the clinical uses of doxorubicin have been limited due to its serious cardiotoxic effects, which are likely the result of generation of free radicals and lipid peroxidation. S-Allylcysteine (SAC), an organosulfur compound purified from garlic, has been reported to have antioxidant and radical scavenging effects. Thus, we examined the effect of SAC on doxorubicin toxicity in mice. Severe doxorubicin toxicity was induced in mice by a single intraperitoneal injection (15 mg/kg body weight). SAC (30 mg/kg) was injected intraperitoneally daily for 5 days, starting two days prior to the administration of doxorubicin. Body weight was measured every alternate day. A measurement of serum creatine phosphokinase (CPK) and a histopathological analysis of the heart and liver was performed 6 days after the administration of doxorubicin. Death of any of the animals was recorded during the observation period. Doxorubicin injection induced a mortality rate of 58%, with SAC treatment reducing the doxorubicin-induced mortality rate to 30%. The severe body weight loss caused by doxorubicin (13%) was also significantly attenuated by SAC treatment (9%). Although an elevation of the level of serum CPK was observed following doxorubicin injection (5472 +/- 570 i.u./L), treatment with SAC significantly reduced the level of CPK (1923 +/- 635 i.u./L). Histological analysis demonstrated that heart and liver damage was significantly less severe in SAC treated mice than in mice receiving only doxorubicin. These results suggest that SAC research may ultimately lead to a resolution of the adverse effects of doxorubicin treatment in cancer chemotherapy.

Animals↗
PubMed2006

The contribution of Aeromonas salmonicida extracellular products to the induction of inflammation in Atlantic salmon (Salmo salar L.) following vaccination with oil-based vaccines.

Intraperitoneal injection of Atlantic salmon with oil-based vaccines often results in severe side effects. Aeromonas salmonicida subspecies salmonicida, a primary antigen in the vaccines, produces extracellular products (ECPs) that are included in the formulation but the role of ECPs in inducing side effects is not well understood. In the present study, we evaluated the contribution of ECPs to early inflammatory reactions since early events determine the outcome of inflammation. Five groups of Atlantic salmon pre-smolts were injected intraperitoneally with one of the following preparations: (1) A. salmonicida water-in-oil (w/o) containing standard amounts of ECPs; (2) A. salmonicida (w/o) with ECPs concentrated five times; (3) A. salmonicida (w/o) without ECPs (ECPs were removed by washing and re-suspension of the bacteria prior to formulation); (4) w/o only (without antigens), and (5) physiological saline. Tissue sections of the injection site (pyloric caeca and surrounding areas) were collected at monthly intervals for 4 months in phosphate buffered formalin and processed for light microscopy. Computer-assisted microscopy with the help of Image Pro analysis program was used to measure the area of inflammation on H&E stained sections. Differential cell counts of leucocytes involved in the inflammatory reaction were also done based on morphology. Overall results show that fish injected with vaccines containing concentrated amounts of ECPs displayed a higher average area of inflammation compared to all other groups. In contrast, washed preparations induced mild reactions compared to vaccines containing either standard or concentrated ECPs. Mild, non-persistent reactions were observed in the group injected with oil adjuvant only. Neutrophils were persistent in inflammations induced by all preparations except w/o only. No inflammatory reactions were observed in the group injected with PBS. The results suggest that ECPs are pro-inflammatory in Atlantic salmon. It is anticipated that ECPs are more readily exposed to inflammatory cells than the bacterial cells themselves during early stages of inflammation because of their orientation at the water-oil interface. The results indicate that ECPs of A. salmonicida play an important role in the induction of early inflammatory reactions. It is also documented that the combination of antigens with oil adjuvants, and not the adjuvants alone, is the inducer of strong inflammatory reactions in Atlantic salmon.

Aeromonas salmonicida↗
PubMed1991

[The depressor effect of antihypertensive factor from rat erythrocytes].

This study observed the depressor effects of erythrocyte antihypertensive factor (AHF) from spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats on SHR, renal hypertensive rats (RHR) and their control animals. Blood pressure (BP) tests were carried out in two parts. Chronic experiment: Six-month-old male rats weighing 200-300 g were divided into six groups: (1) Stroke prone SHR (SHRsp, n = 5); (2) WKY (n = 4); (3) RHR (n = 4); (4) Wistar (n = 4). The rats in each group were given intraperitoneal injections of AHF (10 mg/100 g BW) once. The rats in groups (5) and (6) were injected with normal saline as control. BP was measured just prior to injection and at 0.5, 1, 3, 6, 24 h and 24 h intervals thereafter. BP in SHRsp dropped (from 180.0 +/- 11.5 to 145.0 +/- 12.6, P less than 0.05). Within 24 h there was a further reduction, and the average value of the fall was 65 mmHg (P less than 0.01). BP remained significantly depressed for 4 days and did not recover until the seventh day. In contrast to the effect of this extract on SHR, the BP in WKY rats did not appear to be affected. Normal saline injected intraperitoneally did not lower BP in either SHRsp or WKY rats. BP in RHR rats showed a profound decrease within 3 h, with the average value for the drop being 56 mmHg (P less than 0.001). BP recovered to normal at 6 h. Acute group: Three SHRsp rats with BP 180.0 +/- 5.8 mmHg and weighing 231.0 +/- 11.2 g were anesthetized with sodium pentobarbital. AHF was injected into the femoral vein (0.35 mg/100 g BW). The results showed that the BP markedly decreased after administration of the extract, and the average value for the drop was 35 mmHg (P less than 0.05). The BP did not show any obvious change after injection of WKY rat extract.

Animals↗
PubMed1981

Protection of mice against mouse hepatitis virus by Corynebacterium parvum.

C57BL/6 mice that are highly susceptible to infection with mouse hepatitis virus type 3 were protected against intraperitoneal viral infection by simultaneous intraperitoneal injection of Corynebacterium parvum. No protection was observed when C. parvum was given intravenously or when it was injected intraperitoneally 3 days before viral infection. Protective effects were, however, consistently found when C. parvum was given 2 h before or 2 h after viral infection. Activity was seen only against 10 50% lethal doses and not against 100 50% lethal doses. C. parvum also caused a significant decrease of virus type 3. These data suggest a direct effect of C. parvum on virus-susceptible cells. Injection of C. parvum in mice caused activation of natural killer (NK) cells and of interferon production. However, these two effects were equally demonstrable at high and low doses of C. parvum, whereas protection against mouse hepatitis virus type 3 was not demonstrable at low doses of C. parvum. Thus, antiviral protection may be dissociated from activation of NK cells and induction of interferon.

Animals↗
PubMed1991

Influence of diabetes on the gonadotropin response to the negative feedback effect of testosterone and hypothalamic neurotransmitter turnover in adult male rats.

The influence of diabetes on the gonadotropin response to the negative feedback effect of testosterone (T) and hypothalamic neurotransmitter turnover rates in adult male rats was evaluated. Adult male Sprague-Dawley rats were made diabetic by an intraperitoneal injection of streptozotocin (STZ; 5 mg/100 g body weight) in citrate buffer. Vehicle-injected rats served as controls. On day 9, all rats were bilaterally castrated and treated subcutaneously on alternate days with either peanut oil or T propionate (TP) in peanut oil (100 micrograms/rat). Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and T concentrations were measured by specific radioimmunoassays from blood samples collected on day 1 (before castration) and 2, 4, 6, and 7 days after castration. On day 7 after castration (day 15 after vehicle or STZ treatment), 1 h before autopsy, the rats were injected intraperitoneally with saline or a tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (25 mg/100 g BW), for the measurement of norepinephrine (NE) and dopamine turnover in median eminence and medial basal hypothalamus (MBH). Circulating FSH, LH, PRL, and T levels were significantly lower (FSH and T: p less than 0.001; LH and PRL: p less than 0.05) in gonad-intact rats treated with STZ than in vehicle-injected animals. The castration-induced increase in plasma LH levels was attenuated in diabetic rats. The suppressive effect of T on LH secretion was significantly greater (p less than 0.001) in STZ-treated rats relative to TP-treated nondiabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Systemic and local cytokine profiles in endotoxin-induced preterm parturition in mice.

OBJECTIVE: Our purpose was to determine whether endotoxin-induced preterm parturition is preceded by a change in the maternal serum and amniotic fluid concentrations of tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha. STUDY DESIGN: C3H/HeN pregnant mice at 15 days of gestation (70% gestation) were randomized to receive an intraperitoneal injection of phosphate-buffered saline solution or lipopolysaccharide (50 micrograms/mouse). Blood (n = 93) and amniotic fluid (n = 58) were collected at 1, 4, and 10 hours after lipopolysaccharide injection. Tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha were determined with sensitive and specific enzyme-linked immunoassays. RESULTS: The injection-to-delivery interval was shorter in mice injected intraperitoneally with 50 micrograms lipopolysaccharide than in phosphate-buffered saline solution-treated mice (median 15.5 hours, range: 10 to 105 hours vs median 88.5 hours, range: 53 to 105 hours; p < 0.001). In comparison with phosphate-buffered saline solution-treated mice, a distinct serum cytokine pattern was observed in lipopolysaccharide-treated mice. Concentrations of tumor necrosis factor-alpha were detectable 1 and 4 hours after lipopolysaccharide injection (median 874 pg/ml, range: < 100 to 8000 pg/ml, p < 0.001; and median 263 pg/ml, range: < 100 to 927 pg/ml, p < 0.001, respectively). Concentrations of interleukin-6 were elevated at 1, 4, and 10 hours (median 11.8 ng/ml, range: 6 to 500 ng/ml, p < 0.001; median 27.1 ng/ml, range: 4.5 to 192 ng/ml, p < 0.001; median 1.95 ng/ml, range: < 0.05 to 35 ng/ml, p < 0.015, respectively). Concentrations of interleukin-1 alpha were significantly increased 4 hours after lipopolysaccharide injection (median 102 pg/ml, range: < 15 to 306 pg/ml, p < 0.001). A cytokine pattern distinct from serum was observed in amniotic fluid of lipopolysaccharide-treated mice. In comparison with controls, concentrations of interleukin-6 were significantly elevated 4 and 10 hours after treatment with lipopolysaccharide (median 0.88 ng/ml, range: 0.40 to 2.7 ng/ml, p < 0.025; and median 4 ng/ml, range: 1.9 to 33.6 ng/ml, p < 0.001, respectively). Interleukin-1 alpha was elevated 10 hours after lipopolysaccharide treatment (median 185.3 pg/ml, range: 38 to 511 pg/ml, p < 0.015). Tumor necrosis factor-alpha was not significantly increased in amniotic fluid. CONCLUSION: Preterm delivery after lipopolysaccharide administration is preceded by the appearance of dramatic increases in maternal serum concentrations of tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha and in amniotic fluid concentrations of interleukin-6 and interleukin-1 alpha.

Amniotic Fluid↗
PubMed2004

Effects of cytokines on carbon tetrachloride-induced hepatic fibrogenesis in rats.

AIM: To observe the possible effects of transforming growth factor (TGF) beta(1), interleukin (IL)-6, tumor-necrosis factor (TNF) alpha and IL-10 on experimental rat hepatic fibrosis. METHODS: One hundred SD rats were divided randomly into the three groups. Control group received intraperitoneal injection of saline (2 ml/kg(-1)), twice a week. Fibrogenesis group was injected intraperitoneally with 50% carbon tetrachloride (CCl(4)) (2 ml/kg(-1)) twice a week. Fibrosis-intervention group was given IL-10 at a dose of 4 microg/kg(-1) 20 minutes before CCl(4) administration from the third week. At the fifth, seventh, and ninth weeks, 7 to 10 rats in each group were sacrificed to collect serum. Levels of TGF-beta(1), TNF-alpha, IL-6 and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA). The liver tissues were taken for routine histological examination. RESULTS: Hepatic fibrosis was developed with the injection of CCl(4). Values of the circulating TGFbeta(1), TNFalpha, IL-6 and IL-10 in the control group were 25.49+/-5.56 ng/L(-1), 15.18+/-3.83 ng/L(-1), 63.64+/-13.03 ng/L(-1) and 132.90+/-12.13 ng/L(-1), respectively. Their levels in the CCl(4)-intoxication group were 31.13+/-6.41 ng/L(-1), 18.91+/-5.31 ng/L(-1), 89.08+/-25.39 ng/L(-1) and 57.63+/-18.88 ng/L(-1), respectively, and those in the IL-10-intervention group were 26.11+/-5.32 ng/L(-1), 13.99+/-1.86 ng/L(-1), 74.71+/-21.15 ng/L(-1) and 88.19+/-20.81 ng/L(-1), respectively. A gradual increase was observed in the levels of TGFbeta(1), TNFalpha and IL-6 during hepatic fibrogenesis. These changes were partially reversed by simultaneous administration of IL-10. The histological parameters, characterized by CCl(4)-intoxification, also seemed to be improved with IL-10 treatment, the collagen production was reduced at the ninth week and the histological activity index was decreased from 7.9+/-1.2 to 4.7+/-0.9. CONCLUSION: TGFbeta(1), TNFalpha and IL-6 may play important roles during CCl(4)-induced hepatic fibrogenesis, and IL-10 may counterbalance their effects.

Animals↗
PubMed1992

Growth hormone exerts hematopoietic growth-promoting effects in vivo and partially counteracts the myelosuppressive effects of azidothymidine.

Recombinant human growth hormone (rhGH) was administered to mice to determine its effect on hematopoiesis. BALB/c mice and mice with severe combined immune deficiency (SCID), which lack T cells and B cells, were administered intraperitoneal injections of rhGH for 7 days. Upon analysis, both strains of mice exhibited an increase in splenic and bone marrow hematopoietic progenitor cell content and cellularity, indicating that rhGH can act as a hematopoietic growth factor. C57BL/6 mice were then placed on azidothymidine (AZT). AZT is a reverse transcriptase inhibitor currently used as a treatment for acquired immune deficiency syndrome (AIDS), but which also produces significant myelotoxic effects. Treatment of mice with rhGH partially counteracted the myelosuppressive properties of AZT. Bone marrow cellularity, hematocrit values, white blood cell counts, and splenic hematopoietic progenitor cell content were all significantly increased if rhGH (20 micrograms injected intraperitoneally every other day) was concurrently administered with AZT. Administration of ovine GH (ovGH), which, unlike rhGH, has no effect on murine prolactin receptors, also prevented the erythroid-suppressive effects of AZT in mice, but had no significant effect on granulocyte counts. Thus, the effects of GH are mediated at least in part through GH receptors in vivo. Additionally, when mice were initially myelosuppressed by several weeks of AZT treatment, the subsequent administration of ovGH resulted in an increase in splenic hematopoietic progenitor cells. No significant pathologic effects were observed in mice receiving either repeated rhGH or ovGH injections. Thus, GH exerts significant direct hematopoietic growth-promoting effects in vivo and may be of potential clinical use to promote hematopoiesis in the face of myelotoxic therapy.

Animals↗
PubMed2002

Neutrophils and the calcium-binding protein MRP-14 mediate carrageenan-induced antinociception in mice.

BACKGROUND: We have previously shown that the calcium-binding protein MRP-14 secreted by neutrophils mediates the antinociceptive response in an acute inflammatory model induced by the intraperitoneal injection of glycogen in mice. AIM: In an attempt to broaden the concept that neutrophils and MRP-14 controls inflammatory pain induced by different type of irritants, in the present study, after demonstrating that carrageenan (Cg) also induces atinociception in mice, we investigated the participation of both neutrophils and MRP-14 in the phenomenon. METHODS: Male Swiss mice were injected intraperitoneally with Cg and after different time intervals, the pattern of cell migration of the peritoneal exudate and the nociceptive response of animals submitted to the writhing test were evaluated. The participation of neutrophils and of the MRP-14 on the Cg effect was evaluated by systemic inoculation of monoclonal antibodies anti-granulocyte and anti-MRP-14. RESULTS: Our results demonstrate that the acute neutrophilic peritonitis evoked by Cg induced antinociception 2, 4 and 8 h after inoculation of the irritant. Monoclonal antibodies anti-granulocyte or anti-MRP-14 reverts the antinociceptive response only 2 and 8 h after Cg injection. The antibody anti-MRP-14 partially reverts the antinociception observed after 4 h of Cg injection while the anti-granulocyte antibody enhances this effect. This effect is reverted by simultaneous treatment of the animals with both antibodies. After 4 h of Cg injection in neutrophil-depleted mice a significant expression of the calcium-binding protein MRP-14 was detected in the cytoplasm of peritoneal macrophages. This suggests that the enhancement of the effect observed after treatment with the anti-neutrophil antibody may be due to secretion of MRP-14 by macrophages. It has also been demonstrated that endogenous opioids and glucocorticoids are not involved in the antinociception observed at the 4th hour after Cg injection. CONCLUSION: These data support the hypothesis that neutrophils and the calcium-binding protein MRP-14 are participants of the endogenous control of inflammatory pain in mice despite the model of acute inflammation used.

Analgesia↗
PubMed1997

Induction of Fos-like immunoreactivity in the lower brainstem and the spinal cord of the rat by intraperitoneal administration of an endogenous satiety substance, 2-buten-4-olide.

Induction of Fos in neurons by intraperitoneal injection of 2-buten-4-olide (2-B40), an endogenous satiety substance, was studied immunohistochemically in the brainstem and spinal cord of the rat. Rats injected intraperitoneally with 2-B40 (100 mg/kg) were allowed to survive for 2 h before perfusion. Fos-like immunoreactivity was observed in neurons of the intermediolateral nucleus, ventral reticular formation, lateral reticular nucleus, nucleus of the solitary tract, locus coeruleus, lateral parabrachial nucleus and dorsal raphe nucleus, as well as in tyrosine hydroxylase-immunoreactive neurons of the cell groups A1, A2, A5, A6, A7, C1, C2 and C3.

4-Butyrolactone↗
PubMed1994

Inhibitory effect of melatonin on cataract formation in newborn rats: evidence for an antioxidative role for melatonin.

We evaluated the inhibitory effect of melatonin, a recently discovered scavenger of free radicals, on cataract formation in the newborn rat. The glutathione synthesis inhibitor, buthionine sulfoximine (BSO) (3 mmol/kg), was intraperitoneally injected into newborn rats for 3 consecutive days starting on day 2 after birth. These glutathione depleted rats develop cataracts. Melatonin (4 mg/kg) was injected intraperitoneally into half of the rats once a day beginning at day 2 after birth; the other half of the animals received solvent daily. The incidence of cataract was observed on day 16, after the eyes of the newborn animals had opened. Both reduced glutathione (GSH) and oxidized glutathione (GSSG) levels were measured. Cataracts were observed in all animals (18/18) treated with BSO plus solvent. The incidence of the cataract in the animals cotreated with melatonin was only 6.2% (1/15). Total lenticular glutathione (GSH + GSSG) levels in BSO only treated rats were reduced by 97%. The total glutathione in the lens of the BSO plus melatonin group was significantly higher (by 3%) than that of the BSO only group. The percentage of the total glutathione as GSSG for the BSO plus solvent group was higher than the control value. Cotreatment of BSO injected rats with melatonin (4 mg/kg/day) clearly reduced cataract formation proving that it is directly or indirectly protective against oxidative stress which accompanies glutathione deficiency. The inhibitory effects of melatonin on cataract formation in this study could be due to melatonin's free radical scavenging activity or due to its stimulatory effect on glutathione production.

Animals↗
PubMed2000

Recombinant mistletoe lectin (rML) is successful in treating human ovarian cancer cells transplanted into severe combined immunodeficient (SCID) mice.

The main active constituents carrying the anti-cancer activities of aqueous mistletoe extracts have recently been identified as the mistletoe lectins (MLs). Although three different isolectins have been isolated from plant extracts, molecular biological techniques have revealed the presence of one gene only. Subsequently, recombinant mistletoe lectin (rML) has become available and the aim of the present study was to analyse its anti-cancer potential. SoTü 3 human ovarian cancer cells (2x10(7)) were injected intraperitoneally into SCID mice, while rML treatment was started on the following day. Three experimental groups (n=20 SCID mice) each received every working day an intraperitoneal injection of 30, 150, 500 ng rML per kg body weight, respectively, while 20 SCID mice in the control group received the vehicle solution only. The survival of the animals was taken as the principal outcome measure. In addition, the peritoneal cavity was searched for the presence of tumour cells. Animals were sacrificed when the weight increase due to the development of ascites exceeded 120% of the initial body weight. The treatment continued until day 83 and the surviving animals were sacrificed 84 days after inoculation. In the control group, only two animals survived and were free of tumour at the end of the experiment at 84 days. In contrast, thirteen animals in the 500 ng/kg rML group were still alive and no evidence for the presence of tumour cells in the peritoneum was found. Both, number of animals surviving and survival time were larger in this treatment group. The 30 ng/kg rML group showed an increased number of survivors, whilst the 150 ng rML per kg body weight group revealed the worst survival rates. The results of the present study indicate that rML has potent anti-tumour activity, if administered locally into the peritoneum of a human ovarian cancer harbouring SCID mouse. RML is a macromolecule and its instillation into the peritoneal cavity seems to be particularly effective to inhibit intraperitoneal growth of cancer cells. One explanation might be that altered glycosylation of the cancer cells leads to an increased affinity of rML towards tumour cells. Clinical studies with post-operative instillation of rML in ovarian cancer patients should, therefore, be encouraged to provide clinical evidence for the effectiveness of rML treatment.

Animals↗
PubMed1997

Involvement of endogenous kinins in the pathogenesis of peptidoglycan-induced arthritis in the Lewis rat.

OBJECTIVE: To investigate the pathophysiologic roles of endogenous bradykinin (BK) and des-Arg9-BK on local and systemic inflammatory responses in a rat model of acute arthritis induced by peptidoglycan-polysaccharide (PG-APS). METHODS: Female Lewis rats were injected intraperitoneally with PG-APS. Selective antagonists of B1 (Lys-[Leu8]-des-Arg9-BK) and B2 (Hoe 140) receptors were infused at 500 microg/kg and 5 mg/kg per day for 6 days, starting 3 days before induction of inflammation, with subcutaneous micro-osmotic pumps. The local inflammatory response was assessed by paw edema, joint swelling, and tissue content of BK and des-Arg9-BK. These peptides were measured by highly sensitive and specific chemiluminescent enzyme immunoassays. Systemic inflammatory reaction was evaluated by the hepatic concentration of the type 2 acute-phase protein T-kininogen. RESULTS: PG-APS induced significant paw edema and joint swelling 24-72 hours after intraperitoneal injection. The maximal responses to PG-APS observed at 72 hours were significantly reduced (31-38%) by the combination of both B1 and B2 receptor antagonists at 5 mg/kg per day. PG-APS induced a significant increase of BK (up to 5.3-fold) and des-Arg9-BK (up to 4.1-fold) 72 hours after challenge. Liver T-kininogen content was increased by 5.3-, 7.7-, and 5.8-fold at 24, 48, and 72 hours, respectively, after PG-APS injection. At 24 hours, Hoe 140 and Lys-[Leu8]-des-Arg9-BK increased liver T-kininogen content by 43% and 45%, respectively, but they had no effect at 72 hours. CONCLUSION: The results indicate that endogenous kinins are involved in local and systemic acute inflammatory responses, through both B1 and B2 kinin receptors, in the model of PG-APS-induced arthritis.

Acute Disease↗
PubMed1990

Supplemental putrescine reverses ethanol-associated inhibition of liver regeneration.

Biosynthesis of the polyamines, putrescine, spermidine and spermine, is required for DNA synthesis and liver regeneration after partial hepatectomy. Chronic ethanol consumption impairs polyamine synthesis during the prereplicative phase after partial hepatectomy. To determine whether this delay in polyamine synthesis contributes to ethanol's inhibition of liver regeneration, the ability of supplemental putrescine to improve regeneration in ethanol-fed rats was tested. Chronically ethanol-fed rats and isocalorically maintained controls underwent partial hepatectomy and were injected intraperitoneally with saline or putrescine (0.03 or 0.30 mmol/kg) at 0, 4, 8 and 12 hr after partial hepatectomy. Rats were killed at 24, 48 or 72 hr, 1 hr after exposure to [3H]thymidine, so that DNA synthesis could be estimated. DNA synthesis was significantly inhibited in ethanol-fed rats treated with saline compared with saline-treated pair-fed controls. Supplemental putrescine did not affect DNA synthesis in pair-fed rats. In contrast, putrescine significantly improved [3H]thymidine incorporation 24 to 72 hr after partial hepatectomy in ethanol-fed rats. Intraperitoneal injection of putrescine (1.2 mmol/kg) at the time of partial hepatectomy increased hepatic polyamine concentrations for the first 6 hr after partial hepatectomy despite significantly inhibiting the activity of ornithine decarboxylase, the rate-limiting enzyme for polyamine synthesis, in both groups. Hepatic polyamine levels after putrescine injection were greater in ethanol-fed rats than in similarly treated controls. These data suggest that putrescine treatment triggers events that normalize DNA synthesis in ethanol-fed rats. These results confirm the hypothesis that ethanol's antiregenerative mechanism intimately involves inhibition of putrescine synthesis.

Animals↗
PubMed1981

Human melanoma growth in the peritoneal cavity of the athymic mouse--a model for in vivo study of cell-mediated immunity.

Intraperitoneal injections of 2 X 10(7) SH-Me cells (human metastatic melanoma cells)( to 20 Balb/c nu/nu mice (Group A) and 1 X 10(7) cells to 20 mice (Group B) were performed. All animals were studied clinicopathologically. Five animals in Group A were sacrificed serially, revealing marked tumor growth of the melanoma within the peritoneal cavity. These tumors grew in multiple nodular configurations and tumor ascites was present by the third week. The remaining 15 animals in Group A were allowed to progress and seven subsequently died with mouse viral hepatitis (MVH). These animals had suppressed tumor growth. The remaining eight animals died of peritoneal carcinomatosis with survival time of 24.1 +/- 5.0 days. Eight of the animals in Group B died of mouse viral hepatitis while the remainder died of peritoneal tumor without distant metastasis. Survival time in these animals was 23.8 +/- 2.6 days. Both 2 X 10(7) and 1 X 10(7) tumor cells injected intraperitoneally will constantly produce tumor nodules in non-MHV-infected nude mice with similar survival. This experimental model has proven useful for in vivo study to assess the immunoreactivity of melanoma patient cells reactive against target tumor cells.

Animals↗
PubMed1992

Cyclosporin reduces proteinuria in rats with aminonucleoside nephrosis.

The effect of cyclosporin (CS) was assessed in Sprague-Dawley rats with puromycin aminonucleoside (PA) nephrosis induced by a single intraperitoneal injection of PA. Three groups of rats were injected intraperitoneally with CS (10 mg/kg body weight) daily, beginning 1 day before PA administration, or 5 or 10 days after PA administration, for 10 days. CS significantly reduced proteinuria in rats with PA nephrosis in comparison with untreated nephrotic controls. After discontinuation of the CS treatment, proteinuria gradually increased, reaching values similar to those in control nephrotic rats. CS pretreatment did not prevent the induction of PA-induced nephrotic syndrome. Light microscopy and assessment of anionic sites in the glomerular basement membrane revealed no differences between normal rats, nephrotic controls, and CS-treated rats. These results show that CS can reduce proteinuria in PA nephrosis, but cannot ameliorate the glomerular changes.

Animals↗
PubMed1996

Microglial cell responses to fetal ventral mesencephalic tissue grafting and to active and adoptive immunizations.

Microglia express cytokines, major histocompatibility (MHC) loci, and several other immunologically important constituents. The aim of this study was to detect immunological responses of microglial cells following allogeneic dopaminergic transplantation using active and adoptive immunizations. Adult inbred Fisher 344 (F344 RT1) rats were unilaterally dopamine (DA) depleted in striatum by injection of 6-hydroxydopamine. The degree of degeneration was assessed by recording the rotational response to apomorphine. Fetal ventral mesencephalic tissue containing DA neuroblasts from Wistar-Furth (WF, RT1u) rat donors (9-12 mm CRL) were later implanted in striatum on the lesioned side. Lymph nodes and spleen cells were collected aseptically, resuspended, and diluted for isovolumetric injections. Animals selected for active immunization were injected intraperitoneally with varying amounts of WF lymphocytes. Animals selected for adoptive immunization (transferred immunity) were intraperitoneally injected with 10(8) F344 lymphocytes prepared from animals actively immunized 3 weeks previously. Monoclonal antibodies against CD4 (OX38), CD8 (OX8), CD11b (OX42), MHC class I (OX18), monomorphic MHC class II (OX-6), and ED1 and polyclonal antibodies against tyrosine hydroxylase (TH) were used for immunohistochemistry. We found that the degree of ED1-positive cell proliferation was well correlated to the immunization patterns. Groups that were actively immunized with or without prior adoptive immunization had a larger amount of reactive microglial proliferation. ED1 immunohistochemistry revealed patterns of immunolabeling of engrafted areas: 8-12 weeks after grafting in nonimmunized and adoptively immunized groups reactive microglial proliferation occurred only at the graft periphery. Active and adoptive + active immunization led to ED1-IR within the grafts themselves. At early stages nonimmunized groups had an ED1 pattern which was partially inside the grafts. At early time points nonimmunized groups contained ameboid microglial cells within the grafts which disappeared at later stages and were absent in the immunized groups. ED1-positive ameboid microglial cells within the grafts may be of graft origin and constitute a part of a continued normal development of the fetal tissue.

Animals↗