Allotransplantation of rat parathyroid glands: Effects of organ culture and transplantation into the adrenal gland

Summary Allotransplantation of fresh, 1 or 2 week cultured parathyroid glands from Wistar rats (AgB²) to Fischer rats (AgB¹) resulted in prompt rejection of the transplant in the muscle site; whereas transplantation into the adrenal site offered slightly prolonged survival, suggesting that the latter is a privileged transplantation site.Acknowledgments. The authors thank Mrs Barbara Lovett for her secretarial assistance.     

Effect of pretreatment with acetylsalicylate on surgical bleeding and peroperative mortality in rats undergoing kidney transplantation.

42 rats were pretreated with L-ASA before kidney transplantation, 43 rats acted as controls. 9 rats with L-ASA, but no control rats, died with i.p. haemorrhage. However, in animals surviving the operation, the intraoperative blood loss did not differ significantly between the 2 groups.     

Effect of pretreatment with acetylsalicylate on surgical bleeding and peroperative mortality in rats undergoing kidney transplantation

Summary 42 rats were pretreated with L-ASA before kidney transplantation, 43 rats acted as controls. 9 rats with L-ASA. but no control rats, died with i.p. haemorrhage. However, in animals surviving the operation, the intraoperative blood loss did not differ significantly between the 2 groups.     

Effect of some derivatives of naphthalene on aryl hydrocarbon (Benzo[a]pyrene) hydroxylase in vitro

Résumé L'effet du naphthalène et certains de ses dérivés a été étudié in vitro sur l'action de l'aryl hydrocarbon (benzo[a]pyrene) hydroxylase. Les isomères naphthylphosphordicloridat-(1), naphthylphosphordicloridat-(2) et 2-methyl--naphtothioazol inhibent l'enzyme dans les microsomes des rats controles et des rats traités avec le méthylcholanthrène, sans un effet différentiel. Cette inhibition suggère l'occupation du site commun sur l'enzyme. Cependant le naphtalène, le naphthol-(1), le naphthol-(2) le naphthonitrile-(1), le naphthonitrile-(2) ont un effet negligeable sur l'activité enzymatique.     

Effect of methyl palmitate on the survival of skin semi-allografts in rats

Summary In experiments with rats, the immunosuppressive effect of methyl palmitate on survival of skin semiallografts was proved. Methyl palmitate was applied in a single dose 1 day prior to transplantation.     

Verlängerte Überlebenszeit von Hauthomotransplantaten bei Mäusen durch ein Methylhydrazinderivat

Summary Extended survival of skin homografts in mice was obtained by treatment with a methylhydrazine derivative (1-methyl-2-p-(isopropylcarbamoyl)-benzylhydrazine hydrochloride), representative of a new class of cytotoxic agents. Administration of 100 mg/kg prior to and continuously after the transplantation led to similar survival times as when 300 mg/kg was given daily only after the transplantation. In mice, the compound seems to be more effective than most of the drugs so far known to suppress transplantation immunity.     

Differential expression of genes for uncoupling proteins 1, 2 and 3 in brown and white adipose tissue depots during rat development

The different expression patterns of genes for uncoupling proteins (UCPs) 1, 2 and 3 (ucp1, ucp2 and ucp3) were studied in interscapular brown adipose tissue (BAT) and in four white adipose tissue (WAT) depots (epididymal, inguinal, mesenteric and retroperitoneal) in male rats of different ages (18 days-12 months). UCP mRNA expression levels were determined by Northern blotting. In BAT, there were high levels of expression of UCP1 and UCP3 mRNA, but no detectable levels of UCP2 mRNA. Both ucp1 and ucp3 followed a similar expression pattern with age, with high levels in suckling rats which decreased to 50% or less in rats just under 2 months old, declining thereafter until 5 months and then recovering with age. However, an additional peak of expression was observed for ucp3 at the age of 3 months. In WAT, ucp1 expression was rare: occasional expression was found for UCP1 mRNA in the retroperitoneal depot in suckling rats and in the epididymal and inguinal depots in suckling and mature adult rats. ucp2 and ucp3 had different developmental expression patterns, but these were similar for each gene in the different depots studied. UCP3 mRNA was highly expressed in rats soon after birth, it decreased until 3 months, and increased thereafter, except for the mesenteric WAT where ucp3 expression decreased until 7 months before recovering. The fact that changes with age of both ucp1 and ucp3 expression have a similar profile in BAT, which is also similar to the ucp3 and also ucp1 profiles in some WAT depots, might reflect a common regulatory pattern for the expression of these genes, and also a common function. In contrast to ucp1 and ucp3, ucp2 had a peak of expression at about 2 months, and lower expression at 3 months, suggesting different regulation and probably a different role for this UCP.     

Methimazole treatment reduces cardiac hypertrophy and mortality without a concomitant reduction in blood pressure in established Goldblatt two-kidney one clip hypertension.

The effects of methimazole, an antithyroid drug, on blood pressure and other parameters were evaluated in the established phase of Goldblatt two-kidney one clip (G2K-1C) hypertension. Methimazole was administered via drinking water for five weeks, starting five weeks after hypertension had been induced. After this period of treatment, similarly high blood pressures were observed in methimazole-treated and non-treated G2K-1 C rats, despite the fact that a hypothyroid state had been achieved in methimazole-treated rats. Methimazole-treated G2K-1 C rats showed reductions in heart rate, ventricular weight, ventricular/body weight ratio and mortality in comparison with rats not treated with methimazole. These results clearly demonstrate that hypothyroidism induced by methimazole: a) does not reverse G2K-1 C hypertension, but b) improves the rate of survival and c) reduces relative cardiac hypertrophy, possibly by the reduction in cardiac work observed in Goldblatt hypothyroid rats.     

Methimazole treatment reduces cardiac hypertrophy and mortality without a concomitant reduction in blood pressure in established Goldblatt two-kidney one clip hypertension

The effects of methimazole, and antithyroid drug, on blood pressure and other parameters were evaluated in the established phase of Goldblatt two-kidney one clip (G2K-1C) hypertension. Methimazole was administered via drinking water for five weeks, starting five weeks after hypertension had been induced. After this period of treatment, similarly high blood pressures were observed in methimazole-treated and non-treated G2K-1C rats, despite the fact that a hypothyroid state had been achieved in methimazole-treated rats. Methimazole-treated G2K-1C rats showed reductions in heart rate, ventricular weight, ventricular/body weight ratio and mortality in comparison with rats not treated with methimazole. These results clearly demonstrate that hypothyroidism induced by methimazole: a) does not reverse G2K-1C hypertension, but b) improves the rate of survival and c) reduces relative cardiac hypertrophy, possibly by the reduction in cardiac work observed in Goldblatt hypothyroid rats.     

Transplantation of neural tissues in the brains of laboratory mammals: technical details and comments.

Various technical details on the transplantation of the embryonic neural tissues in the brains of the neonatal and adult rats are presented. Conditions determining successful or leading to unsuccessful survival, growth and differentiation of these transplants are critically examined.     

Culture in low levels of oxygen enhances in vitro proliferation potential of satellite cells from old skeletal muscles

The proliferation ability of satellite cells (considered the 'stem cells' of mature myofibers) declines with increasing age when cultured under standard cell culture conditions of 21% oxygen. However, actual oxygen levels in the intact myofiber in vivo are an order of magnitude lower. No studies to date have addressed the issue of whether culturing satellite cells from old muscles under more 'physiologic' conditions would enhance their proliferation and/or differentiation ability. Therefore, we analyzed satellite cells derived from 31-month-old rats in standard cultures with 21% O₂ and in lowered (∼3%) O₂. Under the lowered O₂ conditions, we noted a remarkable increase in the percentage of large-sized colonies, activation of cell cycle progression factors, phosphorylation of Akt, and downregulation of the cell cycle inhibitor p27^Kip1. These data suggest that lower O₂ levels provide a milieu that stimulates proliferation by allowing continued cell cycle progression, to result ultimately in the enhanced in vitro replicative life span of the old satellite cells. Such a method therefore provides an improved means for the ex vivo generation of progenitor satellite cell populations for potential therapeutic stem cell transplantation. Received 20 April 2001; received after revision 28 May 2001; accepted 31 May 2001     

Reduction of acute toxicity of cyclophosphamide and X-rays by the new immunomodulating compound BM 12.531.

BM 12.531, the 2-[2-cyanaziridinyl-(1)]-2-[2-carbamoylaziridinyl-(1)]-propane, (prop. INN Azimexon), reduces significantly the acute toxicity of cyclophosphamide and X-rays in rats and mice, respectively. The leucopenia induced by X-rays was partially compensated by BM 12.531 in rats.     

Renal effects of a high unsaturated fat diet in renal artery stenosis in rats

The renal effects of an unsaturated fat (UNSAT) diet in mild to moderate two-kidney, one-clip (2K1C) renovascular hypertension were evaluated. An UNSAT diet (37% by energy) prevented the development of hypertension compared to 2K1C rats fed a high saturated fat (SAT) (37% by energy) and a normal fat (CONTROL) (11% by energy) diet. Urinary sodium and fractional sodium excretion increased in 2K1C rats as compared to SHAM operated controls, regardless of the diet received. In the early weeks of the experiment (weeks 2–4 post-surgery to induce hypertension), an enhanced natriuresis occurred in the 2K1C UNSAT as compared to the 2K1C CONTROL and SAT diet groups. This resulted from an increase in the glomerular filtration rate (GFR in mls·min^–1) as measured using the single-injection [⁵¹Cr] EDTA method (2K1C UNSAT; 1.99±0.18 versus 2K1C SAT; 1.27±0.09, p<0.02; and versus SHAM CONTROL; 1.45×0.01; p<0.02). The increased GFR was not associated with alterations in effective renal plasma flow (ERPF) as measured using the single-injection [¹²⁵I] Na hippurate method. No differences in sodium excretion; GFR; ERPF or renal blood flow (microsphere technique) were noted between the 2K1C UNSAT and SAT diet groups at weeks 6–8 post-surgery, despite a continued antihypertensive effect of the UNSAT diet. Hence, the antihypertensive effect of an unsaturated fat diet in 2K1C renovascular hypertension in rats is associated with transient glomerular changes leading to an enhanced natriuresis.     

Thymectomy modifies androgenizing effects of a testis transplant during critical period for neuroprogramming.

Thymectomy simultaneous with transplantation of a syngeneic testis from a littermate to Fischer 344 rats ameliorated the androgenizing effects of the testis transplant on ovarian morphology at 90 days of age.     

Effect of acetylsalicylate on surgical bleeding, postoperative mortality and allograft survival in rats undergoing heart transplantation.

18 rats were treated with L-ASA before heart transplantation and daily thereafter until death or rejection. 22 animals acted as controls. A significantly higher post-operative mortality rate, without any significant modification of the transplant survival time, was found in L-ASA-treated group.     

Copper binds the carboxy-terminus of trefoil protein 1 (TFF1), favoring its homodimerization and motogenic activity

Trefoil protein 1 (TFF1) is a small secreted protein belonging to the trefoil factor family of proteins, that are present mainly in the gastrointestinal (GI) tract and play pivotal roles as motogenic factors in epithelial restitution, cell motility, and other incompletely characterized biological processes. We previously reported the up-regulation of TFF1 gene in copper deficient rats and the unexpected property of the peptide to selectively bind copper. Following the previous evidence, here we report the characterization of the copper binding site by fluorescence quenching spectroscopy and mass spectrometric analyses. We demonstrate that Cys58 and at least three Glu surrounding residues surrounding it, are essential to efficiently bind copper. Moreover, copper binding promotes the TFF1 homodimerization, thus increasing its motogenic activity in in vitro wound healing assays. Copper levels could then modulate the TFF1 functions in the GI tract, as well as its postulated role in cancer progression and invasion.     

Aging and endothelin-1 induced vascular contractions

Contractions produced by endothelin-1 (0.3-30 nM) have been investigated in aorta, renal arteries and mesenteric arteries from 2- and 24-month-old Sprague-Dawley rats. In senescent rats the EC50 values of endothelin-1 for aorta and renal artery were significantly increased (aorta: from 6.2 to 12 nM; renal artery: from 5.2 to 7.8 nM). For mesenteric artery the EC50 value (4.3 nM) was unchanged by aging, whereas the maximal contractile response to endothelin-1 was enhanced (from 8.3 to 11.7 mN). In contrast, there was no significant age-related difference in the maximal endothelin-1 response of aorta and renal artery. The present data demonstrate a reduced sensitivity for aorta and renal artery and an enhanced maximal response to endothelin-1 in the mesenteric artery in senescent rats.     

Transplantation of neural tissues in the brains of laboratory mammals: Technical details and comments

Summary Various technical details on the transplantation of the embryonic neural tissues in the brains of the neonatal and adult rats are presented. Conditions determining successful or leading to unsuccessful survival, growth and differentiation of these transplants are critically examined.Supported by Research grants NS. 08817 and CA. 14650 from N.I.H.     

Thymectomy modifies androgenizing effects of a testis transplant during critical period for neuroprogramming

Summary Thymectomy simultaneous with transplantation of a syngeneic testis from a littermate to Fischer 344 rats ameliorated the androgenizing effects of the testis transplant on ovarian morphology at 90 days of age.Supported by a Morseman Fellowship, NIH grants HD07097, AM21137 and NSF-RIAS grant SER77-06922.     

Trichinella spiralis: acceleration and inhibition of cyst calcification in rats.

Daily administration of vitamin D3 (75,000 IU/kg b. wt) for 7 days accelerated Trichinella spiralis cyst calcification in rats with a 14-week-old infection. When disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered (50 mg/kg b. wt) from 2 days before until 2 days after vitamin D3 treatment, cyst calcification was inhibited. Thus, the ability to inhibit E. spiralis calcification has demonstrated for the first time.