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We have developed a murine model to investigate the pathogenesis of acquired ocular toxoplasmosis. Tachyzoites of PLK strain of Toxoplasma gondii were intracamerally inoculated under anesthesia into the right eyes of naive or perorally preinfected C57BL/6 and MRL-MpJ mice. Clinical and histopathological observations of responses to intraocular infection were analyzed. Ocular inflammation from Toxoplasma gondii is dose-dependent in both strains of mice. After inoculation of fifty parasites, no evidence of inflammation was observed in the eyes of naive mice. The eyes of naive mice that received 500 or 5,000 parasites developed inflammatory changes by day 6 post challenge. By day 8, the changes progressed to moderate to severe intraocular inflammation. Histologic analysis of the ocular lesions demonstrated mononuclear cell infiltration and necrosis predominantly in the anterior segment of the eyes of the naive mice. Inoculation of 50,000 tachyzoites induced a destructive ocular inflammatory response and was uniformly lethal to the mice by approximately one week after challenge. In contrast, eyes from mice previously orally infected with Toxoplasma gondii and that received a 50 or 500 parasite intracameral challenge revealed no inflammation, but the eyes receiving 5,000 parasites demonstrated necrotic focal retinochoroiditis with vitreitis by day 8 after challenge. The murine model reproduces some features of ocular toxoplasmosis in humans and may be suitable for large-scale controlled studies of the pathogenesis and therapeutics of acquired ocular toxoplasmosis as well as for study of the mechanisms of immune privilege in the eye. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical outcomes of on-pump total arterial revascularization with bilateral radial artery (BRA) and left internal mammary artery (LIMA) as conduits in coronary artery bypass grafting (CABG) patients with left ventricular dysfunction (LVD). Methods: All the perioperative medical records and follow-up results of coronary artery disease patients with left ventricular ejection fraction (LVEF) ≤ 40% undergoing CABG from 24 heart centers of 15 provinces and autonomous regions in China between July 2015 and December 2019 were retrospectively analyzed. Results: A total of 87 consecutive patients (55 males and 32 females) underwent on-pump CABG with BRA and LIMA, with a mean age of (57.5±9.1) years old. There were 22 patients complicated with primary hypertension, 12 with diabetes mellitus, 8 with peripheral vascular disease, 7 with chronic obstructive lung disease, 12 with mild renal injury and 3 with partial aortic calcification. There were 43 cases with in-stent stenosis, and 21 had left main disease. The mean LVEF and left ventricular end-diastolic diameter (LVEDD) was (35.5±7.3)% and (65.5±2.6) mm, respectively. The mean graft number, aortic cross-clamp time and cardiopulmonary bypass duration was 3.2±0.9, (90.5±22.7) min and (113.4±19.2) min, respectively. There were 32 mitral and 9 aortic valve replacements, and 5 tricuspid annuloplasties. Prophylactic intra-aortic balloon pumps were implanted in 27 patients. There were 2 operative deaths from acute heart failure. After surgery, there were 15 cases of atrial fibrillation, 1 case of acute kidney injury, 1 case of acute myocardial infarction, and 1 cases of stroke. All the patients fulfilled the follow-up, with a mean time of (39.5±7.7) months. At 3 months after surgery, LVEDD was decreased and LVEF was improved significantly compared with pre-operative indicators [(53.0±1.5) mm vs (65.5±2.6) mm, t= 9.51 P= 0.02; (45.2±3.3)% vs (35.5±7.3)%, t= 13.79, P= 0.001]. No major cardiac events were reported during the follow-up. At (30.5±7.4) months after surgery, 62.4% of patients (53/85) underwent coronary CT angiography examination, and the results indicated that the graft patency was 98.8%, with only one case of RA occlusion occurred. Conclusion: In selected patients of LVD, on-pump total arterial revascularization with BRA and LIMA conduits was proved to be safe and effective.

Objective: To evaluate the mid-term outcomes of bilateral radial artery (BRA) grafts in coronary artery bypass grafting (CABG). Methods: All perioperative medical records and follow-up results of CABG with BRA grafts in multi-centers of China were analyzed retrospectively. Results: A total of 211 patients (170 males and 41 females) underwent CABG grafting with BRA conduits between August 2013 and September 2018, with a mean age of (56.5±9.7) years old (rang 41 to 73 years). There were 161 cases of triple-vessel disease and 50 cases of two-vessel disease. Ninety patients had diabetes mellitus (DM), 35 patients with peripheral vascular disease, 4 patients with chronic obstructive pulmonary disease and 11 with heart valve disease. Two patients underwent off-pump CABG and 209 patients accepted on-pump CABG with commitment valve surgery. There were 210 cases of total arterial revascularization and 161 cases using left thoracic artery conduits, with a graft number of 2-4 (2.7±0.9). No operation-related death occurred, atrial fibrillation happened in 12 patients, hemothorax in 7 cases, and forearm hematoma in one case, hypoxemia in 13 cases and pneumonia in one case. The duration of mechanical ventilation was (8.3±4.7) hours and the mean hospital length of stay was (7.1±2.9) days. Follow-up was completed in 191 patients (90.52%) with a duration of 3-59 (35.5±9.3) months. The mean left ventricular ejection fraction at 3 months after operation was significantly improved, compared to that of the pre-operation (61.0%±7.2% vs 47.1%±5.3%, P= 0.017). All patients survived, except that one died from brain injury. No major cardiac events occurred, with a cumulative survival rate of 100% at 1 year and 99.53% at 3 year after operation, respectively. It was showed in coronary CT angiography (CTA) examination that all grafts in 132 patients were patent at the mean follow-up duration of (21.5±6.4) months. Conclusions: BRA grafts as arterial conduit in CABG are proved to be safe, easy for total arterial revascularization and have good mid-term clinical results.

The mechanism of colonic phosphate absorption is not well defined. We measured unidirectional phosphate fluxes across rat distal colon epithelium in the absence of transepithelial electrochemical gradients. Steady-state mucosal-to-serosal flux (Jms) was not different from the serosal-to-mucosal flux (Jsm), generating no net flux (Jnet = Jms - Jsm, was not different from "0'). Simultaneous fluxes of mannitol, a paracellular probe, exhibited an identical flux pattern, suggesting that phosphate flux across the colonic epithelium may be mediated through the paracellular pathway. Tight junction permeability was increased with mucosal addition of taurodeoxycholate (TDC, 2 mM) which caused a prompt increase in transepithelial conductance from 7.03 +/- 0.35 to 13.88 +/- 0.35 mS/cm2 (p < 0.001). This was associated with an increase in Jsm, but no change in Jms, for mannitol, resulting in a net flux in the secretary direction. Identical TDC-induced changes were observed in phosphate fluxes, again suggesting phosphate permeation through the intercellular, mannitol pathway. A significant correlation was observed between the permeability of phosphate and the permeability of mannitol, measured both in the mucosal-to-serosal and the serosal-to-mucosal directions and under both control and experimental (mucosal TDC) conditions. Thus, colonic phosphate transport is mediated through the paracellular pathway and enema with high phosphate concentrations (1,760 times blood concentration), can trigger rapid and massive phosphate absorption through this diffusive pathway.

Chronic lead exposure may cause hypertension in normotensive rats. This hypertensinogenic effect has been attributed to perturbations in the renin-angiotensin axis, the contractile response of the vascular smooth muscle, or the intracellular Ca2+ homeostasis as a consequence of the inhibition of Na(+)-K(+)-ATPase activity. In this study we examined the short-term effect of lead exposure on blood pressure, plasma renin activity, vascular contractility, and renal Na(+)-K(+)-ATPase activity and abundance in the spontaneously hypertensive rat. Our data indicate that modest lead exposure caused blood pressure elevation within two weeks in this rat strain that is genetically susceptible to the development of hypertension. This rapid blood pressure-elevating effect did not appear to depend on the mechanisms described in hypertension associated with more chronic lead exposure listed above. This acute model provides an additional approach to the study of lead-induced hypertension.

The role of parathyroid hormone (PTH) in ammonium metabolism in the rat remnant kidney was studied by examining the effects of parathyroidectomy (PTx) in rats with intact kidneys and with 5/6 nephrectomy (Nx). PTx in rats with intact kidneys caused a rise in urine pH and a decrease in urinary ammonium excretion without affecting in vitro ammonium production rate or the ammonium content in the cortex. Unexpectedly, the ammonium content in the medulla was markedly reduced by PTx so that the corticomedullary ammonium gradient was inverted. As compared to control rats, rats with 5/6 Nx had a lower urinary ammonium excretion rate, a higher in vitro ammonium production rate, and an increase in ammonium content in both cortex and medulla with reduced corticomedullary ammonium gradient. PTx in rats with 5/6 Nx led to a further decrease in urinary ammonium excretion, attenuated the increase in the in vitro ammonium production rate, and lowered the ammonium content in both cortex and medulla with inverted corticomedullary ammonium gradient. These effects of PTx in Nx rats were corrected by continuous PTH infusion with Alzet minipump. In summary, results from these studies indicate that PTH plays an important role in maintaining the urinary ammonium excretion. In rats with intact kidneys, PTH contributes to urinary ammonium excretion by increasing urinary acidification and medullary ammonium accumulation. In rats with reduced nephron mass, PTH enhances urinary ammonium excretion by stimulating ammonium production and retaining medullary ammonium in the remnant kidney.

In rapidly growing neonatal rats, the intestine is insensitive to vitamin D, and Ca absorption is solely mediated through a non-energy-dependent process. Changes in Ca absorption associated with pregnancy and lactation are qualitatively similar in vitamin D-replete and vitamin D-deplete rats. Moreover, in vivo studies in man and the rat have demonstrated that the bulk of Ca absorption is accomplished in the ileum, a segment with limited capacity for active Ca absorption and is relatively insensitive to the action of 1,25-dihydroxyvitamin D. In patients with intestinal bypass operations the degree of Ca malabsorption and bone mineral loss is proportional to the length of ileum, not duodenum or proximal intestine, removed. Bile salts and lactose are examples of agents which can augment vitamin D-independent ileal Ca absorption through the intercellular pathway.

Convincing evidence for the stimulatory action of 1,25-dihydroxyvitamin D (1,25(OH2)D) on transcellular absorption of calcium (Ca) and inorganic phosphate (P) has led to the consensus that this hormone is the major regulator of Ca and P absorption. Careful review of the literature, however, suggests important regulation of Ca and P absorption by factors and agents other than those mediated by vitamin D. Thus, in rapidly growing neonatal rats, the intestine is insensitive to vitamin D and Ca absorption is entirely mediated through passive mechanisms. Patterns of change in Ca absorption associated with pregnancy and lactation are identical in vitamin D-replete and vitamin D-deplete rats. The presence of active Ca and P absorption in young, growing rats rigidly deprived of vitamin D and of active Ca and P secretion in mature rats optimally replete with vitamin D, also suggests the participation of non-vitamin D factors in the regulation of intestinal Ca and P absorption. The possibility that Ca and P in the peri-enterocyte environment may regulate their own absorption is discussed. Kinetic analysis of 1,25(OH2)D-induced transport mechanisms indicates that saturation would occur at low substrate concentrations, thus raising the question whether these mechanisms would have major regulatory roles under normal dietary conditions. There is also suggestive evidence indicating that even under conditions of low dietary Ca or P intake, the adaptive changes in intestinal absorption may not be mediated by vitamin D alone. Bile salts, lactose and prolactin are discussed as examples of agents which can stimulate Ca and/or P absorption through vitamin D-independent mechanisms.

Combination chemotherapy utilizing high-dose vinblastine, bleomycin, and cisdichlorodiammineplatinum(II) (CDDP) is effective treatment for metastatic testicular cancer. Unfortunately, it is frequently associated with serious toxicity. In a series of 14 patients receiving 65 treatment cycles, several variables were examined as putative risk factors for prediction of serious toxicity. These included drug dose normalized to body weight or surface area, interval since previous cycle, prior therapeutic experience with either radiation therapy or other cytotoxic chemotherapy, and Karnofsky performance status. The strongest determinant of serious toxicity was the vinblastine dose calculated according to body weight. The next most influential prognostic variables were the performance status and a history of previous treatment with either radiation therapy or chemotherapy. Serious toxicity may be anticipated at a frequency of 40% when vinblastine is administered at a total dose of 0.36 mg/kg with bleomycin and CDDP. In our group of patients, the nephrotoxicity of CDDP appeared to be cumulative despite intensive diuresis at the time of administration. Pulmonary toxicity was not observed. Modest reductions in vinblastine dose, especially in patients with poor performance status or a history of previous radiation or other chemotherapy, will substantially lower the frequency of serious toxicity.