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Biomedical subjects

S Y Lin

Publications and source records attributed to S Y Lin.

At least 325 records · Page 18Linked to original sources

Prevention of reflex natriuresis after acute unilateral nephrectomy by neonatal administration of MSG.

Acute unilateral nephrectomy (AUN) results in natriuresis from the remaining kidney through reflex pathways involving the central nervous system and requiring an intact pituitary gland. The natriuresis is accompanied by an increase in the plasma concentration of a peptide or peptides derived from the N-terminal fragment (NTF) of proopiomelanocortin. We measured plasma immunoreactive NTF-like material (IR-NTF) before and after AUN in control rats and rats treated neonatally with monosodium glutamate (MSG), a procedure that produces neuroendocrine dysfunction by destroying cell bodies in the hypothalamic arcuate nucleus, median eminence, and other brain regions. In control rats, IR-NTF increased from 85.8 +/- 54.9 (SD) to 207 +/- 98.1 fmol/ml after AUN (P less than 0.02) as sodium excretion (UNaV) doubled. In MSG-treated rats, AUN produced no change in plasma IR-NTF concentration (58.8 +/- 21.3 vs. 68.3 +/- 18.5 fmol/ml (P = NS), nor did UNaV increase. Tissue content of IR-NTF was reduced in the arcuate nucleus and anterior lobe of pituitaries from MSG-treated rats compared with controls, but was no different in the neurointermediate lobe. These results indicate that the hypothalamic lesion produced by neonatal administration of MSG prevents both the increase in plasma IR-NTF concentration and the natriuresis after AUN, and therefore lend further support to the concept of a causal relationship between these two consequences of AUN.

Animals↗

A gamma-melanocyte stimulating hormone-like peptide causes reflex natriuresis after acute unilateral nephrectomy.

Previous studies have shown that acute unilateral nephrectomy stimulates sodium (UNaV) and potassium (UKV) excretion by the remaining kidney through reflex pathways requiring an intact pituitary gland, and the natriuresis is accompanied by an increase in the plasma concentration of a peptide or peptides derived from the adrenocorticotropic hormone-beta-endorphin precursor molecule pro-opiomelanocortin. We tested the hypothesis that gamma-melanocyte stimulating hormone (gamma-MSH) was such a peptide involved in the postnephrectomy natriuresis. In six rats undergoing sham nephrectomy, no change in UNaV or UKV occurred and plasma immunoreactive gamma-MSH-like material was 40 +/- 18 (SD) fmol/ml 2 hours after the sham procedure. In 10 rats undergoing acute unilateral nephrectomy, UNaV and UKV from the remaining kidney increased significantly, and immunoreactive gamma-MSH was 81 +/- 36 fmol/ml (p less than 0.02). In individual studies, the increase in UNaV after nephrectomy correlated with the postnephrectomy concentration of immunoreactive gamma-MSH (r = 0.75, p less than 0.001). In 17 rats injected with serum or globulin from control rabbits, unilateral nephrectomy led to the expected increases in UNaV and UKV. In 23 rats injected with serum or globulin from rabbits immunized against gamma-MSH, no postnephrectomy natriuresis occurred and the kaliuresis was blunted. In hydropenic, mineralocorticoid-treated rats, intravenous infusion of synthetic gamma-MSH led to natriuresis and kaliuresis with no change in inulin clearance; pretreatment with rabbit anti-gamma-MSH antiserum blocked this effect of peptide infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Inclusion complexation of warfarin with cyclodextrins to improve some pharmaceutical characteristics.

Inclusion complexation of warfarin and alpha- or beta-cyclodextrins in water and in the solid phase were studied by a solubility method, a membrane permeation study, thin-layer chromatography, a dissolution study, IR spectroscopy and differential scanning calorimetry. The solubility of warfarin increased with the addition of cyclodextrins. The apparent stability constants of the alpha- and beta-cyclodextrin complexes are 10.29 M-1 and 148.88 M-1, respectively. The greater the stability constant of the inclusion complex the lesser the permeability of warfarin. Solid complexes of warfarin and alpha- or beta-cyclodextrins were obtained by freeze-drying. Clear differences in IR absorption spectra and DSC thermograms were observed between the inclusion complexes and physical mixtures. The dissolution rate of the freeze-dried warfarin-cyclodextrin complexes was increased about 1200-fold and 550-fold for alpha- and beta-cyclodextrins, respectively. The dissolution rate of warfarin was significantly improved by complex formation.

Calorimetry, Differential Scanning↗

Novel method for the preparation of controlled-release theophylline granules coated with a polyelectrolyte complex of sodium polyphosphate-chitosan.

A novel method for the preparation of theophylline granules coated with a polyelectrolyte complex of sodium tripolyphosphate and chitosan was developed. The theophylline granules containing sodium tripolyphosphate were stirred in an HCl solution of chitosan. During the mixing, the dissolved sodium tripolyphosphate in the granule moved to the surface and reacted with the chitosan, resulting in the formation of the polyelectrolyte complex film. The factors affecting the drug content, the particle size, and the coating-film thickness of the resultant coated granules were determined. The theophylline content in the coated granule decreased with increasing content ratio of sodium tripolyphosphate to theophylline in the original granule and with increasing chitosan concentration in the coating solution. The coated granule size increased with increasing chitosan concentration in the coating solution and with decreasing agitation speed. The coating-film thickness increased with an increase in the chitosan concentration, the pH of the coating solution, and the sodium tripolyphosphate to theophylline content ratio in the original granule. The drug-release pattern of the coated granules followed zero-order kinetics and the release rates were significantly reduced compared with that of the original granule.

Chemical Phenomena↗

Preparations of agglomerated crystals of polymorphic mixtures and a new complex of indomethacin-epirizole by the spherical crystallization technique.

Agglomerated crystals of indomethacin and epirizole were prepared by the spherical crystallization technique. The solvent used was ethanol-water-chloroform, ethyl acetate-water, or ethyl acetate-aqueous sodium chloride. From the ethanol-chloroform-water system, we obtained agglomerated crystals of a polymorphic mixture of the beta form of indomethacin (original form, gamma) and amorphous epirizole. When the mole percent of epirizole loaded into the system was less than 63 and 38% for the ethyl acetate-water and ethyl acetate-aqueous sodium chloride systems, respectively, the agglomerated crystals consisted of a polymorphic mixture of the alpha form of indomethacin and amorphous epirizole. When the respective mole percent of epirizole loaded was more than 65 and 43% in the aforementioned systems, a new complex of indomethacin-epirizole (molecular ratio equal to 2:1) was obtained. Recovery of complex from the drugs loaded in the ethyl acetate-aqueous sodium chloride system was higher than that in the ethyl acetate-water system, as a result of a salting-out effect. The solubility of indomethacin in the agglomerated complex in a solution of 30% aqueous ethanol and in disintegration test solution no. 2 (composition, 0.05 M KH2PO4 plus 0.0236 M, NaOH, pH 6.8), specified in the Japanese Pharmacopeia X (JPX), was higher than in the physical mixture (molecular ratio of indomethacin to epirizole equal to 2:1). In the ethanol solution, indomethacin was transformed into the gamma form during dissolution, and a decrease in solubility occurred. The process of dissolution of the tablet of the agglomerated complex was described by zero-order kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Calorimetry, Differential Scanning↗

Role of the pituitary in reflex natriuresis following acute unilateral nephrectomy.

We studied the role of altered pituitary function in the reflex natriuresis that occurs after acute unilateral nephrectomy (AUN). In normal rats, AUN increased both sodium (UNaV) and potassium excretion within 90 min. In hypophysectomized rats, no increase in cation excretion after AUN occurred, results which were duplicated in rats in which pituitary function was altered by prior treatment with dexamethasone (2 mg/kg ip for 3 days). In adrenalectomized rats, AUN led to increases in cation excretion similar to those seen in normal rats, indicating that intact adrenal function was not necessary for this excretory response following AUN. These changes in cation excretion were correlated with measurements in peripheral plasma of two peptides derived from the pituitary precursor molecule pro-opiomelanocortin (POMC). Radioimmunoassayable plasma beta-endorphin failed to change after AUN in any of the conditions studied. However, a sensitive radioimmunoassay for the N-terminal fragment (NTF) of POMC indicated that plasma NTF rose significantly after AUN in normal and adrenalectomized rats but did not change in hypophysectomized, steroid-pretreated, or shamoperated rats. The increase in NTF concentration correlated with the increase in UNaV after AUN. These results demonstrate that the reflex increase in cation excretion after AUN is dependent on an intact pituitary gland and is associated with an increase in peripheral plasma concentration of NTF. NTF, or some other peptide residing in the N-terminal portion of POMC, could promote the natriuresis after AUN; the importance of the pituitary gland in this response could be the secretion of this peptide.

Animals↗

Centrally administered naloxone blocks reflex natriuresis after acute unilateral nephrectomy.

Acute unilateral nephrectomy (AUN) leads to a natriuresis and kaliuresis by the remaining kidney through reflex mechanisms involving opiate receptors. To determine whether the opiate receptors mediating these responses are located in the central nervous system, we carried out AUN in anesthetized rats undergoing continuous ventriculocisternal perfusion (VCP) with artificial cerebrospinal fluid (CSF). AUN caused large increases in both Na (UNaV) and K (UKV) excretion without changes in glomerular filtration rate or arterial blood pressure. When the opiate receptor antagonist naloxone was added to the perfusate to achieve a perfusion rate of 32 micrograms X kg-1 X h-1, AUN failed to increase either UNaV or UKV by the remaining kidney. This dose of naloxone, however, was without effect when infused intravenously. Addition of thyrotropin-releasing hormone (TRH) to the artificial CSF to achieve a VCP rate of 50 micrograms X kg-1 X h-1 also blocked the expected increase in UNaV and UKV by the remaining kidney after AUN. Infusion of TRH intravenously at the same rate did not interfere with the postnephrectomy natriuresis or kaliuresis. Higher intravenous infusion rates of TRH (1 and 2 mg X kg-1h-1) prevented the postnephrectomy natriuresis without affecting the kaliuresis. These results indicate that the effect of naloxone to block the reflex natriuresis and kaliuresis after AUN resides largely in the central nervous system. The blockade by naloxone of the postnephrectomy natriuresis is duplicated by centrally administered TRH, providing another example of the interaction of this hormone with the endogenous opioid system. Large intravenous infusions of TRH also block the postnephrectomy natriuresis but not the kaliuresis.

Animals↗

Reflex responses to reductions in functioning renal mass.

Both acute unilateral nephrectomy (AUN) and unilateral ureteral obstruction (UUO) result in an acute increase in cation excretion from the contralateral kidney. AUN results in reflex changes in systemic hemodynamics owing to an acute and transient increase in arterial pressure that activates carotid sinus baroreceptors and constitutes an afferent limb in the reflex; hemodynamic adjustments and increased cation excretion result. The reflex involves participation of the endogenous opioid system, with receptors located primarily in the central nervous system, and requires intact pituitary function because both hypophysectomy and pretreatment with large doses of dexamethasone prevent the postnephrectomy natriuresis. The natriuresis is closely correlated with an increase in the plasma concentration of the NH2-terminal fragment of the pituitary peptide precursor molecule proopiomelanocortin, which suggests that such a peptide could participate directly or indirectly in the postnephrectomy natriuresis. Surgical denervation of either the ipsilateral or the contralateral kidney markedly alters the response to AUN, which prevents the natriuresis and blunts the kaliuresis, and indicates a role for renal neural reflexes. Renorenal reflex pathways also mediate the response of the contralateral kidney to UUO, because denervation of either the ipsilateral (obstructed) or the contralateral kidney abolishes both the natriuresis and kaliuresis usually seen after UUO. This reflex also involves the endogenous opioid system, for it does not occur in rats receiving an i.v. infusion of the opiate receptor antagonist naloxone.

Adaptation, Physiological↗