The pharmacokinetics of intraduodenally administered diazepam in rats as influenced by composition of the central lymph

Diazepam, a drug with hydrophobic properties, was used as a model for studying its distribution (after intraduodenal administration) into the central lymph of rats. The intestinal lymph, which prevails in the central lymph, was modified for the presence of total lipids (chylomicrons) by means of fasting, a normal or an artificial diet (olive oil). The lymphatic levels of diazepam exceeded the corresponding blood levels in the fed and oil-fed group; the levels were steady in the fasted group with the exception of the absorption phase of the curves. The kinetic parameters assessed in the blood and lymph of the individual groups obtained by mathematical evaluation of the concentration curves differed because of quantitative differences in the presence of chylomicrons in the lymph. Lymphatic bioavailability in comparison with i.v. administration was found to be substantially lower.     

The pharmacokinetics of intravenously administered diazepam in the rat influenced by composition of the lymph

Diazepam, a drug with hydrophobic properties, was used as a model drug for the study of its distribution after i.v. administration into the central lymph of the rat. The intestinal lymph, which prevails in the central lymph, was modified for the presence of total lipids chylomicrons by fasting and a normal or an artificial diet (olive oil). Lymphatic levels of diazepam in all three experimental conditions exceeded the corresponding blood levels, being lowest in the fasted group, higher in the normally fed animals and highest in the oil-fed group. Experimental blood and lymphatic data were subjected to pharmacokinetic analysis. The changes in the parameters were found to depend quantitatively upon the presence of chylomicrons in the lymph. Lymphatic availability of diazepam in the central lymph is stimulated by an increased content of the chylomicrons fraction of the lymph.     

The intraovarian progesterone modulation of follicle development in the rabbit ovary

Intraovarian progesterone levels were manipulated by surgically adjusting the number of corpora lutea (CL) present in rabbit ovaries and this model was used to study the local effect of luteal progesterone on growth of follicles. The results show that when a single CL or several CL were present, follicle growth was inhibited. However, when all CL on one ovary were removed, increased numbers of follicles grew even when a single CL was present in the contralateral ovary. These findings show that progesterone inhibits follicle growth and that at least part of its action is local, i.e., exerted within the ovary. Additionally, ovarian blood vessels and periovarian lymph ducts were cannulated, and samples were collected and analyzed for steroid and protein content. The results show that when CL were present, ovarian vein progesterone levels were elevated 10-30-fold over levels in ovaries without CL; this high concentration points to the blood vascular system as the principal carrier of the steroid within the ovary. Analysis of lymph showed that protein content was consistently high and that the progesterone concentration was not significantly altered with the presence of CL; these two findings show that ovarian capillaries are extremely permeable to proteins, but the unexpectedly low concentrations of progesterone in lymph may signal an intraovarian countercurrent mechanism by which it is returned to the blood.     

Pharmacokinetics of mitomycin C in cancer patients during prolonged administration of the preparation

The mitomycin C levels in the blood of patients subjected to prolonged intravenous injection of the drug in 200-300 ml of isotonic sodium chloride solution for 15-50 minutes were determined in the microbiological test system consisting of E. coli and 1.5 per cent of agar in the meat-peptone broth with restricted contents of the nutrients. Such administration of the drug usually provided lower blood levels than intravenous injections of the drug in analogous doses. However, the drug renal excretion was also less intensive. It suggested that the drug administered for a prolonged period was more completely absorbed by the host tissues. This was confirmed by much lower blood levels of the drug, when the tumors were large, as compared to those in patients with insignificant residues of the tumor tissue after surgical resections. The curves of mitomycin C distribution in the blood indicate that the pharmacokinetics of the drug in patients with tumors is a multi-factorial function.     

Pharmacokinetic prediction of the efficacy of using sisomicin in wound infections

The pharmacokinetics of sisomicin in the blood, infection foci and urine of patients with wound infections was studied comparatively. Higher blood levels of the antibiotic after intravenous injection as compared to those after intramuscular injection provided its more intensive penetration into the tissues of the wound edges and bottom. After intravenous injection the sisomicin concentration in the tissues was sufficient for inhibition of the strains of Staphylococcus, E. coli and Ps. aeruginosa detected in the patients, while after intramuscular injection the antibiotic levels were sufficient only for inhibition of the first two causative agents. Comparison of the data on the sisomicin pharmacokinetics in the blood and tissues of the wounds provided the characteristics of the level of the drug penetration into the focus of the infection ("therapeutic availability"). Since the levels of sisomicin in the blood and infection foci were highly variable in different individuals. It is recommended that the antibiotic be used under the control of its concentrations in patients. It was shown that the data on the sisomicin renal excretion might be used for the purposes of the pharmacokinetic control.     

Verification of therapeutic levels of procainamide and N-acetyl- procainamide in ventricular arrhythmia]

Therapeutical efficacy was clinically evaluated in 21 patients with ventricular cardiac arrhythmias. The drug was given orally with preceded intramuscular dose. Therapeutic effect was verified by the measurements of procainamide and N-acetylprocainamide concentrations in blood serum to determine the minimal effective concentration of the drug required to obtain satisfactory antiarrhythmic effect. Procainamide proved effective in cardiac arrhythmias in 14 patients (66.7%) with statistical significance in the acute myocardial infarctions; blood serum procainamide plus N-acetylprocainamide levels being were below the therapeutical range. The poor correlation of the dose of the drug and respective procainamide, N-acetylprocainamide concentrations in blood was observed. Relationship of the therapeutical effects blood serum level of the drug should be estimated basing of the assays of both procainamide and N-acetylprocainamide .     

Lymph esterases of the house mouse (Mus musculus)--II. The role of esterase-2 in fat resorption

1. Intralipid infusion into the duodenum of Mus musculus was accompanied by changes in lymph and serum concentrations of two esterase isozymes, ES-1 and ES-2. Whereas ES-1 levels declined in both lymph and serum, ES-2 levels increased 5-fold in lymph within 120 min, and fell to a plateau 3- to 4-fold the fasting level; serum levels of ES-2 increased continually. 2. The changes in lymph ES-2 concentrations were paralleled by lymph triglyceride concentration during Intralipid infusion. Genetically determined differences in the concentration of two allozymes, ES-2B and ES-2D, were reflected in differences in lymph triglyceride levels. The lymph triglyceride concentration was strongly correlated with approximately the cube root of the lymph ES-2 concentration for both allozymes. 3. The source of lymph ES-2 during fat resorption was probably an intracellular jejunal pool; serum ES-2 also re-entered the lymph but this fraction was not influenced by fat resorption. 4. Purified chylomicrons possessed no esterase activity; however, it was postulated that ES-2 plays an essential role in fat resorption and is extruded with the primary chylomicrons from the enterocyte.     

Pharmacokinetics of penicillins in the blood of dogs administered the combination preparation, ampiox, internally]

The pharmacokinetics of penicillins in the blood of dogs treated with ampiox, a combination of ampicillin and oxacillin at a ratio of 1 : 1 was studied. The drug was administered orally in single or repeated doses of 25, 50 and 100 mg/kg. The maximum levels of ampicillin in the blood serum were observed 1 hour after a single administration of the drug. The therapeutic concentrations of the antibiotic were preserved for 6 hours, its value being depended on the dose used. The maximum concentration of oxacillin was detected 1 hour after the drug administration in various doses and it was preserved in the blood at the therapeutic levels for 3 hours. The dynamics of circulation of ampicillin and oxacillin administered separately did not differ from that established for the use of ampiox. The regularities of the pharmacokinetics of ampiox on its repeated use remained practically unchanged.     

Effects of follicle-stimulating hormone on inhibin release by different testicular compartments in the adult ram.

The aim of this study was to determine the bidirectional release of immunoreactive inhibin-alpha (irINH-alpha) by different testicular compartments in the adult ram and to assess the effects of FSH on the distribution of inhibin in the testis. Immunoreactive INH-alpha was measured by RIA in fluid samples collected concurrently from the three testicular compartments--the seminiferous tubules, the interstitium, and the vascular system--through catheters inserted surgically into the rete testis, testicular lymphatic duct system, and spermatic veins, respectively. Overall, the concentration of irINH-alpha in rete testis fluid was 25 times the level in testicular lymph and over 500 times the concentration in peripheral blood. The pattern of irINH-alpha concentration in rete testis fluid was inversely related to that in testicular lymph, but i.v. administration of FSH had a decoupling effect on this relationship by depressing inhibin concentration in testicular lymph without affecting inhibin levels in rete testis fluid. Nevertheless, increased flow of testicular lymph more than compensated for the transient fall in irINH-alpha concentration so that, overall, the total output of inhibin via the testicular lymphatic duct system (and the vascular system) increased significantly. No persistent or significant changes were observed in the flow rate of rete testis fluid or concentration of irINH-alpha in the fluid after administration of FSH. The time frame for the response of the testis to FSH is indicative of the involvement of a mediator. Electrophoretic analysis of serially collected testicular lymph samples consistently revealed an FSH-induced release of a series of proteins in the M(r) range of 30,000-32,000.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Renal Function on Plasma Digoxin Levels in Elderly Ambulant Patients in Domiciliary Practice

An investigation into the relations between the daily dose of digoxin, drug regimen, serum digoxin concentration, and creatinine and digoxin clearance was carried out in a group of elderly ambulant patients in domiciliary practice. Moderate to severe impairment of renal function was found both in patients taking digoxin and in elderly control subjects. Plasma digoxin levels were not related to blood urea concentrations or creatinine clearance. Digoxin clearance was less than creatinine clearance. Now that plasma digoxin levels can be measured relatively easily their estimation should become part of clinical practice.     

Specific activation of lymphocytes against acetylcholine receptor in the thymus in myasthenia gravis

In 13 patients with myasthenia gravis, spontaneous in vitro production of antibody to acetylcholine receptor (AChR) by thymic cells was observed in seven patients, by bone marrow cells in nine, by peripheral blood cells (PBL) in six, and by lymph node cells in nine. The rate of anti-AChR production in culture closely correlated with the serum anti-AChR level. Specific activity of the immunoglobulin (Ig) G spontaneously produced (anti-AChR/total IgG) was about 10-fold higher in the thymus than in bone marrow, peripheral blood, or lymph node cultures. Pokeweed mitogen (PWM) enhanced anti-AChR production only by PBL. With neither thymus nor lymph node cells did PWM stimulate anti-AChR production, although it greatly enhanced total IgG production. In bone marrow, it depressed both, and it appeared that the anti-AChR was derived from long-lived plasma cells that may be responsible for delaying the fall of serum anti-AChR levels after thymectomy. The results suggest that AChR-specific cells are selectively activated in the thymus, and this may help to explain the benefits of thymectomy in myasthenia gravis.     

Flow and composition of lymph from the ovary and uterus of cows during pregnancy

Ovarian or uterine lymph was collected continuously for periods of up to 25 days from 16 cows cannulated at stages of pregnancy ranging from 96 to 278 days post coitum. Blood samples were taken acutely from the ovarian and uterine veins during surgery and periodically from the jugular vein during the course of lymph collection. The flow rate and cell content of lymph was measured and blood and lymph plasma samples were analysed for progesterone, pregnenolone, pregnenolone sulphate, androstenedione, testosterone, oestrone, oestrone sulphate, oestradiol-17 beta, prostaglandin (PG) F-2 alpha, total protein and albumin. There was a high flow rate of protein-rich lymph from luteal ovaries with rates up to 101.7 ml/h occurring in individual lymphatics over short periods. Peripheral ovarian and uterine lymph contained a low concentration of cells (mean less than 10(5) cells/ml) comprising about 82-87% lymphocytes, 11-14% macrophages and monocytes and 2-4% other cells. At all stages of pregnancy, the concentration of progestagens and androgens was higher in ovarian lymph than in uterine lymph or blood plasma. The differences were greatest for progesterone and androstenedione which occurred at 200-fold and 60-fold greater concentration respectively in ovarian lymph than in jugular plasma. When serial 10 min samples were collected over a 12-h period, the concentration and output of progesterone in ovarian lymph varied in a phasic manner, ranging from 3.5 to 7.6 microM and from 31.7 to 293.1 nmol/h respectively. There was a positive correlation between the output of progesterone in lymph and the progesterone concentration in jugular blood samples taken every 20 min. During most of pregnancy there was little difference between the concentration of oestrogens in ovarian lymph, ovarian venous plasma and jugular plasma but, during the 3-5 days before calving, these hormones occurred at slightly higher concentration in ovarian lymph. Apart from pregnenolone and androstenedione, all steroids occurred at lower concentrations in uterine lymph than in jugular plasma. Shortly before parturition there was an abrupt increase in the concentration of PGF-2 alpha in uterine lymph. Lymph reflects more accurately the milieu of tissue cells than efferent blood and further analysis of differences in the concentration of substances in lymph relative to the output in the ovarian and uterine arterial and venous blood may lead to the identification of factors important in local regulatory mechanisms in the reproductive tract.     

Using the lymph fistula rat model to study the potentiation of GIP secretion by the ingestion of fat and glucose

Glucose-dependent insulinotropic polypeptide (GIP) is an important incretin produced in the K cells of the intestine and secreted into the circulating blood following ingestion of carbohydrate- and fat-containing meals. GIP contributes to the regulation of postprandial insulin secretion and is essential for normal glucose tolerance. We have established a method of assaying GIP in response to nutrients using the intestinal lymph fistula model. Administration of Ensure, a mixed-nutrient liquid meal, stimulated a significant increase in intestinal lymphatic GIP levels that were approximately threefold those of portal plasma. Following the meal, lymph GIP peaked at 60 min (P < 0.001) and remained elevated for 4 h. Intraduodenal infusions of isocaloric and isovolumetric lipid emulsions or glucose polymer induced lymph GIP concentrations that were four and seven times the basal levels, respectively. The combination of glucose plus lipid caused an even greater increase of lymph GIP than either nutrient alone. In summary, these findings demonstrated that intestinal lymph contains high concentrations of GIP that respond to both enteral carbohydrate and fat absorption. The change in lymphatic GIP concentration is greater than the change observed in the portal blood. These studies allow the detection of GIP levels at which they exert their local physiological actions. The combination of glucose and lipid has a potentiating effect in the stimulation of GIP secretion. We conclude from these studies that the lymph fistula rat is a novel approach to study in vivo GIP secretion in response to nutrient feeding in conscious rats.     

The diagnostic value of thyroglobulin concentration in fine-needle aspiration of the cervical lymph nodes in patients with differentiated thyroid cancer

INTRODUCTION: Recurrent differentiated thyroid cancer generally occurs first in the neck. Ultrasound is sensitive in detecting enlarged cervical lymph nodes but is not specific enough. Ultrasound-guided fine-needle biopsy increases the specificity but still may fail to detect a recurrence of the disease in the cystic metastatic lymph nodes. The aim of the study was to estimate the value of Tg concentration in the needle washout after fine-needle aspiration of suspicious lymph nodes. MATERIAL AND METHODS: The 105 patients studied had presented one or more enlarged suspicious cervical lymph nodes. All had undergone total thyroidectomy and (131)I ablative therapy. Serum thyroglobulin (Tg) concentration was within the 0.15-711.5 ng/ml range (mean 22.24 ng/ml) and Tg recovery range 94-100%. The positive Tg washout concentration cut-off value was established as equal to the mean plus two standard deviations of the Tg washout concentration of patients with negative cytology. RESULTS: Lymph node involvement was diagnosed by cytology in 15 patients and in 28 lymph nodes. Positive Tg washout concentration was found in 22 patients and in 48 lymph nodes. All the lymph nodes which turned out to have positive cytology had a positive Tg washout concentration. All lymph nodes with positive cytology were positive in pathology. Seven patients and 20 lymph nodes with negative cytology were positive in the Tg washout concentration test. All but one patients and all but two lymph nodes with a positive Tg washout concentration had positive pathology. CONCLUSIONS: 1. Ultrasound-guided fine-needle biopsy is not sensitive enough to detect all metastatic lymph nodes. 2. The Tg washout concentration test is 100% sensitive in the detection of metastatic lymph nodes. 3. Cytology in ultrasound- guided fine-needle biopsy is 100% specific. 4. The Tg washout concentration test carries a risk of false-positive results. 5. Both methods should be used for early detection of metastatic lymph nodes in patients with differentiated thyroid cancer.     

影响骨髓移植术后环孢素A血药浓度的相关因素分析

目的:环孢素A是临床常用的免疫抑制剂,应用于预防骨髓移植术后发生的移植物抗宿主病。环孢素A药代动力学及药效学个体差异大,治疗窗窄,其血药浓度受多种因素影响。本文研究探讨骨髓移植术后患者环孢素A血药浓度,寻找影响其血药浓度变化的可能因素,并为临床上药物使用提供参考依据。方法:以化学发光微粒子免疫分析法测定并记录骨髓移植术后患者应用环孢素A后的血药浓度,并根据环孢素A血药浓度、患者的基本情况(性别、年龄、手术日期等)、用药情况(剂量、给药方式、合并用药等)及相应生化检验结果等,应用SPSS统计软件对数据进行多元线性回归分析,考察环孢素A血药浓度与各生化指标的相关性。结果:环孢素A的单位血药浓度与患者的性别、年龄及体重无明显的相关性,与血浆CHO、AST、BUN、三唑类抗真菌药物具有统计学意义的相关性(P0.05)。结论:环孢素A的血药浓度不仅受自身个体因素的影响,还与给药方式、合用药物情况等外界因素有关。应结合患者的临床表现进行全面分析,建议定期监测血药浓度,及时调整治疗方案,实现个体化给药,使环孢素A在骨髓移植术后的应用得到最佳的治疗效果。     

CEAmRNA在大肠癌患者微转移早期预测中的意义

目的：大肠癌是最常见的恶性肿瘤之一,血行转移是大肠癌根治性手术失败的原因之一,在根治性切除肿瘤患者中,有大部分患者死于肿瘤的复发和转移,因此早期发现大肠癌微转移,对于延长患者预后指导下一步治疗具有重要意义。本研究已检测大肠癌患者外周血和引流静脉血中CEAmRNA的表达,以探索手术操作和微转移的关系,以及引流静脉血中微转移的发生与临床病理因素的关系,探讨早期发现大肠癌血循环微转移的意义。方法：应用逆转录多聚酶链式反应（RT-PCR）法检测大肠癌患者手术前,手术后外周血及引流静脉血液中的CEAmRNA水平。结果：（1）大肠癌患者术前外周血CEAmRNA阳性率26．7％（16／60）,引流静脉血阳性率48.3％（29／60）,引流静脉血明显高于外周静脉血（P〈0．05）。（2）大肠癌引流静脉血中CEAmRNA在肿瘤大于5厘米者、DukesC期、中低分化程度、有淋巴转移者、浸及浆膜者比外周静脉血更有统计学上的意义。（3）手术前后引流静脉血CEAmRNA阳性率具有显著差异（P〈O．05）,外周血CEAmRNA阳性率无显著差异。结论：大肠癌引流静脉血微转移是大肠癌肝转移的发生的早期阶段,引流静脉血CEAmRNA的表达能更早期反映出大肠癌患者微转移的发生,引流静脉微转移发生率与肿瘤分化程度、浸润深度、TNM分期、淋巴结转移、远处转移相关,是反映大肠癌生物学行为的指标之一,手术对大肠癌血循环微转移有促进作用。     

CEA mRNA在大肠癌患者微转移早期预测中的意义

目的:大肠癌是最常见的恶性肿瘤之一,血行转移是大肠癌根治性手术失败的原因之一,在根治性切除肿瘤患者中,有大部分患者死于肿瘤的复发和转移,因此早期发现大肠癌微转移,对于延长患者预后指导下一步治疗具有重要意义。本研究已检测大肠癌患者外周血和引流静脉血中CEA mRNA的表达,以探索手术操作和微转移的关系,以及引流静脉血中微转移的发生与临床病理因素的关系,探讨早期发现大肠癌血循环微转移的意义。方法:应用逆转录多聚酶链式反应(RT-PCR)法检测大肠癌患者手术前,手术后外周血及引流静脉血液中的CEA mRNA水平。结果:(1)大肠癌患者术前外周血CEA mRNA阳性率26.7%(16/60),引流静脉血阳性率48.3%(29/60),引流静脉血明显高于外周静脉血(P0.05)。(2)大肠癌引流静脉血中CEA mRNA在肿瘤大于5厘米者、Dukes C期、中低分化程度、有淋巴转移者、浸及浆膜者比外周静脉血更有统计学上的意义。(3)手术前后引流静脉血CEAm RNA阳性率具有显著差异(P0.05),外周血CEA mRNA阳性率无显著差异。结论:大肠癌引流静脉血微转移是大肠癌肝转移的发生的早期阶段,引流静脉血CEA mRNA的表达能更早期反映出大肠癌患者微转移的发生,引流静脉微转移发生率与肿瘤分化程度、浸润深度、TNM分期、淋巴结转移、远处转移相关,是反映大肠癌生物学行为的指标之一,手术对大肠癌血循环微转移有促进作用。     

The Effects of Dextrothyroxine in Diabetes

Eighteen diabetic patients were treated with dextrothyroxine (from 2 mg to 8 mg daily) for varying periods up to six months. This produced a decided reduction of serum cholesterol levels. Statistically valid comparisons were made of their fasting blood sugar levels before and after two weeks of dextrothyroxine treatment. Administration of this drug was associated with a significant elevation of fasting blood sugar levels. Good diabetic control did not preclude this adverse effect.After more prolonged treatment with the drug, 8 of the 18 patients experienced progressive deterioration of their diabetic control, necessitating increased amounts of insulin or oral drugs. Despite close observation, one patient developed acidosis.When dextrothyroxine was discontinued, there was a significant drop in blood sugar levels in these patients. Two patients had hypoglycemic reaction.When the fasting blood sugar values of the 18 patients, studied while they were receiving significant doses of dextrothyroxine, are compared with a control series of blood sugar determinations obtained on these same patients before dextrothyroxine administration was begun, the diabetogenic effect of this drug is confirmed by the highly significant difference demonstrated.Four patients were given dextrothyroxine a second time, and again experienced deterioration of diabetic control.     

Subcutaneous versus Intravenous Administration of Rituximab: Pharmacokinetics,CD20 Target Coverage and B-Cell Depletion in Cynomolgus Monkeys

The CD20-specific monoclonal antibody rituximab (MabThera^®, Rituxan^®) is widely used as the backbone of treatment for patients with hematologic disorders. Intravenous administration of rituximab is associated with infusion times of 4–6 hours, and can be associated with infusion-related reactions. Subcutaneous administration of rituximab may reduce this and facilitate administration without infusion-related reactions. We sought to determine the feasibility of achieving equivalent efficacy (measured by endogenous B-cell depletion) and long-term durability of CD20 target coverage for subcutaneously administered rituximab compared with intravenous dosing. In these preclinical studies, male cynomolgus monkeys were treated with either intravenous rituximab or novel subcutaneous formulation of rituximab containing human recombinant DNA-derived hyaluronidase enzyme. Peripheral blood samples were analyzed for serum rituximab concentrations, peripheral B-cell depletion, and CD20 target coverage, including subset analysis according to CD21+ status. Distal lymph node B-cell depletion and CD20 target coverage were also measured. Initial peak serum concentrations of rituximab were significantly higher following intravenous administration than subcutaneous. However, the mean serum rituximab trough concentrations were comparable at 2 and 7 days post-first dose and 9 and 14 days post-second dose. Efficacy of B-cell depletion in both peripheral blood and distal lymph nodes was comparable for both methods. In lymph nodes, 9 days after the second dose with subcutaneous and intravenous rituximab, B-cell levels were decreased by 57% and 42% respectively. Similarly, levels of peripheral blood B cells were depleted by >94% for both subcutaneous and intravenous dosing at all time points. Long-term recovery of free unbound surface CD20 levels was similar, and the duration of B-cell depletion was equally sustained over 2 months for both methods. These results demonstrate that, despite initial peak serum drug level differences, subcutaneous rituximab has similar durability, pharmacodynamics, and efficacy compared with intravenous rituximab.     

Comparison of flow rates and composition of ovarian lymph and blood in the day-16 pregnant rat

Rats (5) at Day 16 of pregnancy were anaesthetized and a modification of a venous outflow technique was used to collect ovarian venous blood and lymph for 2 h. Both fluids were analysed for progesterone, 20 alpha-dihydroprogesterone, total protein, transferrin and albumin concentrations. In addition SDS gel electrophoresis was carried out to obtain an initial indication of permeability of capillaries to the various protein fractions. The concentrations of progesterone and 20 alpha-dihydroprogesterone in ovarian lymph were only 37% and 48% respectively of the corresponding concentrations in the venous plasma. Total protein concentration in the lymph was 53% of the venous plasma. The albumin and transferrin concentrations were similarly lower in lymph than plasma but the difference was only significant for transferrin. This study confirms that the rate of lymph flow, per unit mass of tissue, is high for the ovary and represents about 1.1% of plasma flow. It shows also that of the total progestagens secreted only around 0.5% leave by the lymphatic route. The finding of relatively low progestagen concentrations in lymph questions the view that progestagens are transported by simple diffusion from the luteal cell to blood and raises the possibility of a counter-current flow between fluid in the interstitial space and blood.