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Biomedical subjects

S A Falk

Publications and source records attributed to S A Falk.

At least 19 recordsLinked to original sources
PubMed1991

Serial glomerular and tubular dynamics in thyroidectomized rats with remnant kidneys.

Serial measurements were performed in Munich-Wistar rats with five-sixths nephrectomy that had undergone prior selective thyroidectomy (Tx group) or thyroidectomy with thyroxine replacement (TxT4 group) to determine the effects of Tx on glomerular and tubular dynamics in relation to Tx attenuation of renal failure progression. At 1 week, inulin clearance rates (Cin) in TxT4 and Tx rats were 0.367 +/- 0.171 and 0.120 +/- 0.036 mL/min, respectively, different at P less than 0.01. Corresponding single-nephron filtration rate (SNGFR), glomerular plasma flow (QA), glomerular transcapillary hydraulic pressure (delta P), and proximal tubular reabsorption (Jv) were all reduced in Tx compared with TxT4 rats (P less than 0.01). Protein excretion (UPROT) was 151 +/- 40 in TxT4 rats, and 9 +/- 5 mg/d in Tx animals. Glomerular mesangial matrix expansion and focal tubulointerstitial changes were more frequent in TxT4 than Tx rats. By 4 weeks, Cin, SNGFR, QA, glomerular ultrafiltration coefficient (Kf) and Jv were similar in Tx and TxT4. Only glomerular capillary pressure (PGC) remained lower in Tx rats (35 +/- 3 v 50 +/- 3 mm Hg in TxT4, P less than 0.001). UPROT was 161 +/- 24 in TxT4 and 17 +/- 12 mg/d in Tx rats. While 7% +/- 4% of glomeruli showed focal sclerosis in TxT4 rats, there was none in the Tx group. Maximal glomerular planar area increased between 1 and 4 weeks in the TxT4 group, but not in the Tx group. However, this measurement was not significantly different between TxT4 and Tx glomeruli at 1 or 4 weeks. Minimal focal tubulointerstitial changes were found in TxT4, but there were not progressive from those observed at 1 week. The reduced PGC at 1 week was the result of a disproportionately greater increase in afferent (RA) than efferent arteriolar resistance (RE) in Tx rats (P less than 0.025); however, at 4 weeks, both RA and RE had decreased to values identical to those in TxT4 animals and the lower PGC in Tx rats was the result of a reduced mean arterial pressure. In conclusion, a reduced PGC was the sole functional correlate of decreased proteinuria and glomerulosclerosis afforded by Tx in this partial nephrectomy model. Suppression of either nephrectomy-related hypertrophy or tubulointerstitial injury by Tx could not be excluded as at least partially protective factors.

Animals↗
PubMed1991

Atrial natriuretic peptide and dopamine in established acute renal failure in the rat.

Recent studies have shown that atrial natriuretic peptide (ANP) alone or combined with dopamine (D) markedly improved renal function when given immediately after an ischemic insult. However, the potential beneficial effect of ANP or ANP-D in the established phase of acute renal failure (ARF) and the duration of this effect have not been examined. In the present study atriopeptin III (APIII) and D, sufficient to maintain mean arterial pressure between 100 and 110 mm Hg, or normal saline were given i.v. for four hours to awake Munich-Wistar rats (N = 6 each group) two days after ARF induction with intrarenal norepinephrine (NE). Renal function and morphology were then examined two days after treatment (Day 4). Serum creatinine (SCr) was similarly increased in both groups at the time of APIII-D or saline infusion (Day 2). By Day 4 SCr had decreased to the pre-ARF induction level in APIII-D-treated rats (P less than 0.005), but continued to rise in saline-treated animals (P less than 0.025). Day 4 renal blood flow and glomerular filtration rate (GFR) were higher in APIII-D-compared to the saline-treated group (9.13 +/- 1.14 vs. 4.41 +/- 2.25 ml/min and 0.787 +/- 0.066 vs. 0.370 +/- 0.185 ml/min, respectively, both P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1991

Effects of atriopeptin III on isolated rat afferent and efferent arterioles.

The effects of atriopeptin III (AP III) on in vitro prepared afferent (AA) and efferent arterioles (EA) from rat kidneys were tested in a system in which lumen diameter could be measured. AP III (10(-13)-10(-7) M) had no effect on lumen diameter of AA that were not preconstricted. When AA were preconstricted with either angiotensin II (ANG II) or norepinephrine (NE), however, AP III increased lumen diameter in a concentration-dependent manner to the preconstriction baseline value. Maximal vasodilation occurred at 10(-10) M AP III. Unlike AA, EA constricted by 50% to 10(-10) M AP III further constricted EA that were pretreated with ANG II or NE. Dilation in ANG II-preconstricted AA to AP III was not inhibited by indomethacin. Constriction of EA to AP III was not altered by [Sar1-Ala8] ANG II, enalapril, OKY 046, or phentolamine. Results indicate that in isolated renal arterioles AP III dilates preconstricted AA but constricts EA that have either not been pretreated or have been preconstricted with other agonists. The effect of AP III on preconstricted AA does not require vasodilator prostaglandin mediation. The constrictor effect of AP III on EA is not dependent on angiotensin, thromboxane, or alpha-adrenergic mediation.

Angiotensin II↗
PubMed1990

The management of hyperthyroidism. A surgeon's perspective.

Surgery for the treatment of hyperthyroidism is rapid and permanent, highly safe, and highly successful and has an important and complementary role with medical therapy and 131I. In Grave's disease cases total thyroidectomy, performed only if parathyroid glands are preserved, prevents recurrent hyperthyroidism. Bilateral subtotal thyroidectomy or total lobectomy with contralateral subtotal lobectomy are done if at least one parathyroid cannot be preserved on each side. In terms of recurrent laryngeal nerve preservation, all three operations are equally safe if the nerve is positively identified and traced throughout its course.

Antithyroid Agents↗
PubMed1989

Loss of epithelial polarity: a novel hypothesis for reduced proximal tubule Na+ transport following ischemic injury.

Ischemia results in the marked reduction of renal proximal tubule function which is manifested by decreased Na+ and H2O reabsorption. In the present studies the possibility that altered Na+ and H2O reabsorption were due to ischemia-induced loss of surface membrane polarity was investigated. Following 15 min of renal ischemia and 2 hr of reperfusion, proximal tubule cellular ultrastructure was normal. However, abnormal redistribution of NaK-ATPase to the apical membrane domain was observed and large alterations in apical membrane lipid composition consistent with loss of surface membrane polarity were noted. These changes were associated with large decreases in Na+ (37.4 vs. 23.0%, P less than 0.01) and H2O (48.6 vs. 36.9%, P less than 0.01) reabsorption at a time when cellular morphology, apical Na+ permeability, Na+-coupled cotransport, intracellular pH and single nephron filtration rates were normal. We propose that the abnormal redistribution of NaK-ATPase to the apical membrane domain is in part responsible for reduced Na+ and H2O reabsorption following ischemic injury.

Adenosine Triphosphate↗
PubMed1989

The protective mechanism of thyroidectomy in a rat model of chronic renal failure.

Selective thyroidectomy (Tx) has been shown to attenuate proteinuria and disease progression in models of chronic renal failure (CRF). In this investigation, four groups of Munich-Wistar rats were studied to determine if glomerular dynamics or another renal metabolic consequence of Tx was responsible for the protective effect as measured by 24-hour protein excretion (UPROT). The groups were TxT4, thyroxine-replaced Tx rats with five-sixths nephrectomy; Tx, Tx rats not receiving replacement thyroxine with five-sixths nephrectomy; TxI, Tx rats not receiving replacement thyroxine with five-sixths nephrectomy that were given continuous intraperitoneal isoproterenol to restore systemic and renal hemodynamics; and TxT4(C), two-kidney Tx rats receiving replacement thyroxine that served as normal controls. Five-sixths nephrectomy was carried out 2 weeks after Tx, and experiments were carried out 1 week later. Serum T4 was profoundly reduced and there was failure to gain weight in Tx and TxI rats, despite similar protein intakes in all groups. Cardiac output was reduced in Tx, but was similar in TxI to levels in TxT4 rats. Whole-kidney glomerular filtration rate was lower in Tx, at 0.145 +/- 0.052 mL/min (P less than 0.05), but similar in TxI (0.305 +/- 0.147 mL/min) to that in TxT4 rats (0.317 +/- 0.135 mL/min). Twenty-four-hour urinary protein, which was 129 +/- 57 mg in TxT4, was reduced in Tx to 9 +/- 3 mg (P less than 0.01) but restored in TxI to 89 +/- 30 mg, a level similar to that in TxT4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Atrial natriuretic peptide and dopamine in a rat model of ischemic acute renal failure.

Atrial natriuretic peptide (ANP) has been shown to reverse experimental models of ischemic acute renal failure (ARF). However, infusion of ANP has been associated with systemic hypotension making its use in clinical ARF impractical. Therefore, in this investigation, dopamine (D) was combined with intravenous (i.v.) atriopeptin III (AP III) to determine if this regimen was effective in reversing ARF while preventing systemic hypotension and maintaining renal blood flow (RBF). Four groups of Munich-Wistar rats were studied. Group 1, sham-ARF; Group 2, renal artery (RA) clamp (55 min) followed by i.v. saline; Group 3, RA clamp followed by i.v. AP III-D; and Group 4, RA clamp followed by i.v. D only. All infusions were begun after RA clamp release and continued for four hour. Mean arterial pressure in Group 3 rats given AP III-D were similar to that in Group 2, slightly less than that in Groups 1 and 4 (P less than 0.05), but consistently greater than 100 mm Hg during the four hour infusion. RBF in Group 3 was elevated above the level in Group 1 at P less than 0.05. Glomerular filtration rate (GFR), depressed by 52% in Group 2, was corrected to control (sham-ARF) levels in Group 3. In Group 4 there was a small but significant increase in GFR compared to Group 2 (P less than 0.05), but it remained less than that in sham-ARF or AP III-D treated ARF rats (P less than 0.01). Urine flow rate and urine sodium excretion rate were more than sixfold higher in Group 3 than any other group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1989

Ischemia-induced loss of epithelial polarity. Role of the tight junction.

In proximal tubular cells ischemia is known to result in the redistribution of apical and basolateral domain-specific lipids and proteins into the alternate surface membrane domain. Since tight junctions are required for the maintenance of surface membrane polarity, the effect of ischemia on tight junction functional integrity was investigated. In vivo microperfusion of early loops of proximal tubules with ruthenium red (0.2%) in glutaraldehyde (2%) was used to gain selective access to and outline the apical surface membrane. Under control situations ruthenium red penetrated less than 10% of the tight junctions. After 5, 15, and 30 min of ischemia, however, there was a successive stepwise increase in tight junction penetration by ruthenium red to 29, 50, and 62%, respectively. This was associated with the rapid duration-dependent redistribution of basolateral membrane domain-specific lipids and NaK-ATPase into the apical membrane domain. Taken together, these data indicate that during ischemia proximal tubule tight junctions open, which in turn leads to the lateral intramembranous diffusion of membrane components into the alternate surface membrane domain.

Animals↗
PubMed1988

Temporary postthyroidectomy hypocalcemia.

The causes of temporary hypocalcemia after thyroidectomy are not well understood. In 18 patients undergoing unilateral (UL) and bilateral thyroid lobectomy (BL), an attempt was made to preserve all parathyroid glands with an intact blood supply. Total calcium (bound and free), free calcium (physiologically active form), albumin, parathyroid hormone, and calcitonin levels were serially measured. After UL, free calcium, parathyroid hormone, and calcitonin levels were unchanged, but total calcium level decreased because albumin level decreased. After BL, total calcium level decreased due to a decrease in albumin-bound calcium level. Free calcium level also decreased due to a decrease in parathyroid hormone level. Calcitonin level did not change. Despite careful preservation of the parathyroids and their blood supply, BL is frequently associated with temporary hypoparathyroidism. Techniques for preservation of parathyroid glands with their vascular integrity, correlation of surgical manipulation of parathyroids and calcium level, and calcium binding are discussed.

Calcium↗
PubMed1988

Phosphate restriction reduces proteinuria of the uninephrectomized, diabetic rat.

Proteinuria is the clinical hallmark of diabetic nephropathy and the harbinger of progressive renal disease. Therefore, the present study was designed to examine the effect of phosphate restriction on the proteinuria of streptozotocin-induced diabetes mellitus in the rat. Uninephrectomy was performed in experimental and control groups to worsen the degree of diabetic nephropathy. Proteinuria was prevented in Sprague-Dawley rats treated with the intestinal phosphate binder, dihydroxyaluminum aminoacetate (DHAAA) (24.75 +/- 20.35 mg/d at 3 months v control, 77.45 +/- 44.72 mg/d, P less than 0.001); an effect that was independent of protein and caloric intake, plasma albumin and lipids, severity of diabetes, mean arterial pressures, cardiac output, and renal calcium accumulation. The effect of DHAAA on protein excretion and glomerular hemodynamics was examined in similarly prepared Munich-Wistar rats; these rats did not tolerate long-term studies. Three weeks of DHAAA again caused a consistent fall in proteinuria (5.98 +/- 7.28 v 34.94 +/- 24.28 mg/d) and in transmembrane hydraulic pressure difference (41.1 +/- 1.2 v 46.4 +/- 2.8 mm Hg, P less than 0.005). In conclusion, phosphate restriction significantly decreases the proteinuria of Sprague-Dawley and Munich-Wistar uninephrectomized rats with streptozotocin-induced diabetes mellitus. Micropuncture of Munich-Wistar rats suggests that a reduction of intraglomerular pressure may be at least partially responsible for such an effect.

Aluminum Hydroxide↗
PubMed1987

Glomerular dynamics in the hypothyroid rat and the role of the renin-angiotensin system.

Munich-Wistar rats underwent thyroidectomy (TX) with reimplantation of the parathyroid glands. Systemic hemodynamic and micropuncture studies were performed at 1 and 3 wk post-TX, and the results were compared with levothyroxine replaced controls (TXT4). Cardiac output (CO) in TX rats fell progressively and was 40% of that in TXT4 at 3 wk. Renal blood flow declined in parallel with CO. Systemic blood pressure did not fall in TX rats because of a 50% increase in systemic vascular resistance by 3 wk post-TX. Glomerular dynamics were not significantly different between TX and TXT4 rats at 1 wk; however, by 3 wk single-nephron glomerular filtration rate (SNGFR) had fallen to 16.5 +/- 1.1 vs. 34.1 +/- 3.4 nl/min in TXT4 controls (P less than 0.001). In 3-wk TX rats, glomerular plasma flow (QA) was 50.9 +/- 3.7 vs. 108.0 +/- 8.7 nl/min in TXT4 rats (P less than 0.001), net hydraulic ultrafiltration pressure (delta P) was 33 +/- 2 vs. 37 +/- 1 mmHg in TXT4 rats (P less than 0.01), and the ultrafiltration coefficient (Kf) was 0.025 +/- 0.003 vs. 0.084 +/- 0.008 nl X s-1 X mmHg-1 in TXT4 controls (P less than 0.001). Although the changes in systemic and glomerular hemodynamics were progressive over 3 wk, proximal tubular reabsorption fell maximally within 1 wk. Similar patterns of alterations in glomerular dynamics are known physiological consequences of angiotensin II (ANG II).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1986

Glomerular and tubular dynamics in mercuric chloride-induced acute renal failure.

Mercuric chloride (HgCl2)-induced acute renal failure has received considerable investigative attention but little agreement as to its pathogenesis. A source of some disagreement has been the lack of direct glomerular dynamics measurements in this disorder. We examined glomerular dynamics, tubular integrity, and whole kidney function at 24 hours in Munich-Wistar rats given either HgCl2, 3.5 mg/kg, or a similar volume of 0.9% saline solution intramuscularly. Arterial blood pressure was elevated in HgCl2-injected rats, but renal blood flow and its distribution were similar to those of controls. Inulin clearance, however, was reduced by 89% in HgCl2-injected animals. Glomerular dynamics experiments demonstrated similar glomerular plasma flow (QA) and glomerular capillary and tubular pressures in control and HgCl2-injected animals but a higher net afferent ultrafiltration pressure and lower ultrafiltration coefficient (Kf) in the HgCl2-injected group. Single-nephron glomerular filtration rate (SNGFR), when measured from Bowman's space and HgCl2-injected rats, was similar to that measured from late proximal tubules in controls. However, SNGFR determined from the later proximal tubule in HgCl2-injected rats was only one third of that measured from Bowman's space. QA estimated from glomerular counting was similar to that calculated from Bowman's space SNGFR in HgCl2-injected rats. 3H-inulin microinjection experiments confirmed the presence of tubular fluid backleak suggested by the discrepancy in Bowman's space and late proximal tubular SNGFR measurements. It is concluded that at 24 hours in low-dose HgCl2-induced acute renal failure, tubular fluid backleak is the major pathogenetic factor, with a decline in Kf having a potential secondary role.

Acute Disease↗
PubMed1985

Graves' disease associated with histologic Hashimoto's thyroiditis.

The microscopic slides of 16 patients who underwent bilateral subtotal thyroidectomy for hyperthyroid Graves' disease were reviewed and classified into three groups: I, Hashimoto's thyroiditis; II, Graves' disease; and III, both Hashimoto's thyroiditis and Graves' disease. Three patients were classified as group I, 10 as group II, and three as group III. In 38% of the patients with clinical Graves' disease the histologic evidence of Hashimoto's thyroiditis could be found either alone or in combination with histologic evidence of Graves' disease (groups I and III). One patient in group I, four in group II, and three in group III had infiltrative ophthalmopathy (50% of total). Hyperthyroid Graves' disease, Graves' ophthalmopathy, and Hashimoto's thyroiditis can occur all together, in duads, or individually at a specific time in a patient's life.

Adult↗
PubMed1977

Intrarenal dynamics in the pathogenesis and prevention of acute urate nephropathy.

Tubular fluid flow, urine osmolality, and pH were selectively altered to determine the relative protective roles of these factors in a rat model of acute urate nephrophathy. Various prehyper uricemic conditions were established in five groups of animals: (a) normopenic Wistar rats given no pretreatment (Group I); (b) Wistar rats given acetazolamide, 20 mg/kg, and isotonic NaHCO3 to produce urine alkalinization (Group II); (c) Wistar rats in which a moderate diuresis, similar to that observed in Group II but without urine alkalinization, was induced with furosemide, 2 mg/kg (Group III); (d) Wistar rats in which a high-flow solute diuresis was induced with furosemide, 15 mg/kg (Group IV); (e) Brattleboro rats, homozygous for pituitary diabetes insipidus, that had a spontaneous high-flow water diuresis (Group V). A comparable level of hyperuricemia (19.4+/-2.2 mg/100 ml) was achieved in all animals with intravenous urate infusion. Clearance and micropuncture studies were performed before and 1 h after induction of hyperuicemia. Group I rats had mean falls in renal plasma flow and glomerular filtration rate of 83 and 86%, respectively; nephron filtration rate decreased 66%, and tubular and microvascular pressures increased twofold. In Group II there were 45 and 47% declines in renal plasma flow and glomerular filtration rate, respectively, a 66% fall in nephron filtration rate, and a 30% increase in tubular and vascular pressures. Moderate amounts of urate were seen in the kidneys. Group III had changes in renal function identical to Group II suggesting that the moderate prehyperuricemic diuresis in the latter group and not urine alkalinization produced the partial protection observed. Groups IV and V were completely and comparably protected with renal function studies unchanged from controls. It is concluded that high tubular fluid flow, whether induced by a solute or water diuresis, is the primary mechanism of protection in acute urate nephropathy. At most, urine alkalinization plays a minor preventive role.

Animals↗
PubMed1976

A micropuncture study of the early phase of acute urate nephropathy.

The early pathophysiological changes in acute urate nephropathy were investigated in a rat model using micropuncture, clearance, and morphologic methods. Plasma urate was increased from 1.2 +/- 0.6 to 20.1 +/- 3.1 mg/100 ml (P less than 0.001). Urinary urate rose from 24.3 +/- 5.1 to 142.2 +/- 21.0 mg/100 ml (P less than 0.001). Renal plasma flow and glomerular filtration rate fell to 17 and 14% of control values, respectively, and urine flow rate decreased from 11.3 +/- 4.8 to 4.2 +/- 2.2 mul/min (all P less than 0.005) Superficial nephron filtration rate fell less than that of the whole kidney (70 vs. 86%). Both proximal and distal tubular pressures were increased from 10.6 to 26.1 mm Hg and from 7.2 to 24.7 mm Hg, respectively (P less than 0.005). Efferent arteriolar and peritubular capillary pressures were increased twofold. Vascular resistance beyond the peritubular capillaries increased from 4.8 X 10(9) to 21.6 X 10(9) dynes s/cm5. Extensive deposits of uric acid and urate were found in the tubular system and vasa recti from the corticomedullary junction to the tip of the papilla. It is concluded from these experiments that not only tubular obstruction in the collecting ducts, but also obstruction of the distal renal vasculature, are the primary early pathogenetic events in acute urate nephropathy.

Absorption↗