A B S T R A C T We investigated the relationship of the kallikrein-kinin system and the renin-angiotensin system in the regulation of blood pressure, salt and water excretion, and renal blood flow. Normotensive and hypertensive black and white men were studied during unrestricted sodium intake as well as on a 10-meq/day sodium intake; potassium intake was held constant throughout the study (80 meq/day).During unrestricted sodium intake, urinary kallikrein activity was greater in white normotensives than white hypertensives or black normotensives. There was no difference (P > 0.05) between white and black hypertensives or between black normotensives and black hypertensives. All groups had greater urinary kallikrein activity on low sodium vs. unrestricted sodium intake, but the increase in black hypertensives was small, and they excreted significantly less kallikrein than the other groups on the low sodium diet. Plasma renin activity showed similar increments after sodium restriction in all groups. Urinary kallikrein activity correlated with renal blood flow in all groups except the black normotensives on low sodium intake. Renal blood flow could be correlated uniformly with log (urinary kallikrein activity/supine plasma renin activity) in all groups on either diet. Urinary sodium and potassium excretion and urine volume were not different among the groups. We concluide: (a) support the concept that the kallikrein-kinin system and the renin-angiotensin system contribute to the regulation of renal blood flow and may account for racial differences in renal vascular resistance. INTRODUCTIONKallikrein is an enzyme that catalyzes the formation of the vasodilator hormones, lysyl-bradykinin (kallidin) and bradykinin, from a plasma alpha-2 globulin substrate, kininogen (1). Urinary kallikrein appears to be derived from the kidney and differs from the enzyme that circulates in plasma (2). It has been proposed that kallikrein exists in the renal cortex and may occupy a location that is juxtaposed to the enzyme renin (3). Although a physiologic function for lysyl-bradykinin, the enzymatic product, has not been established, pharmacologic infusion studies have shown that the peptide is a natriuretic and vasodilatory compound (4).A number of studies in humans and experimental animals have attempted to determine the relationship between urinary kallikrein activity and blood pressure regulation (5-9). Although most investigators feel that kallikreins could influence blood pressure, the meaning of these findings is controversial. Based on provocative preliminary observations (10) and the aforementioned studies, it seemed appropriate to examine the simultaneous influence of race and blood pressture on urinary kallikrein activity. In addition, we have examined the association between kallikrein in uirine and factors that have been related to blood pressure regulation including urinary volume, soditum excretion, plasma renin activity, and renal blood flow. These latter studies were designed to determine a possible physiologic role ...
The use of BMSC in the Stem Cell Ophthalmology Treatment Study achieved meaningful visual improvements in a significant percentage of the NAION patients reported. Improvements typically manifested no later than 6 months post-procedure. Duration of visual loss did not appear to affect the ability of the eyes to respond to treatment. Possible mechanisms by which visual improvement occurred may include BMSC paracrine secretion of proteins and hormones, transfer of mitochondria, release of messenger RNA or other compounds via exosomes or microvesicles and neuronal transdifferentiation of the stem cells.
Background Premature ovarian failure is a relatively common condition that affects 1–3% of adult women. Premature ovarian failure occurs when there is loss of ovarian function in women younger than 40 years of age. The causes are mostly iatrogenic or idiopathic. Amenorrhea and infertility are the most important clinical manifestations. So far, no therapeutic intervention has been proved effective in restoring fertility in patients with premature ovarian failure. Attempts to stimulate ovarian function through hormone manipulation typically prove unsuccessful, and patients usually resort to egg donation to achieve pregnancy. In our preclinical work, intraovarian administration of human bone marrow–derived mesenchymal stem cells was able to restore ovarian hormone production, reactivate folliculogenesis, and reverse infertility in a chemotherapy-induced ovarian failure mouse model. Case presentation We present two cases of Caucasian women with premature ovarian failure who resumed ovarian estrogen production and menses 7 months following autologous bone marrow–derived mesenchymal stem cell injections into the ovary. This pilot clinical study is registered with ClinicalTrials.gov (identifier NCT02696889 ). In this report, we present data from our first two cases that have completed study procedures so far. The bone marrow–derived mesenchymal stem cells were harvested from the bone marrow of the iliac crest of the patients with premature ovarian failure and nucleated cells concentrated and enriched in bone marrow–derived mesenchymal stem cells intraoperatively, and then injected into the patient’s right ovary via laparoscopy. Autologous bone marrow stem cell engraftment into the ovary resulted in several improvements in the treated patients with premature ovarian failure. In measurements by transvaginal ultrasound, there were increases of approximately 50% in volume of the treated ovaries in comparison with the contralateral control ovaries that persisted to the end of the study (1 year). Serum levels of estrogen increased by approximately 150% compared with the preoperative levels. Each of the two patients had an episode of menses, and also both of them reported marked improvement of their menopausal symptoms that also persisted to the end of the study (1 year). The bone marrow–derived mesenchymal stem cell implantation procedure was very well tolerated with no reported adverse events. Conclusions Our study reveals promising improvement of premature ovarian failure–related clinical manifestations in two patients after intraovarian autologous bone marrow–derived mesenchymal stem cells engraftment. These early observations call for additional assessment and further development of intraovarian bone marrow–derived mesenchymal stem cell injection for possible treatment of patients with premature ovarian failure.
The BMSC protocols of the SCOTS achieved meaningful visual acuity improvements or stability in RP that were of statistical significance. Duration of disease did not appear to affect the ability of eyes to respond. Safety was confirmed. Possible mechanisms by which improvement occurred may include transdifferentiation of BMSC into Neuronal Nuclei (NeuN) positive cells, BMSC paracrine secretions or neurotrophic factors and hormones, transfer of mitochondria, release of messenger RNA or other compounds via exosomes or microvesicles. Given the successful outcome in this otherwise progressive condition, consideration should be given to providing this treatment option.
The long-term consequences of forebrain ischemia include delayed Parkinson's syndrome. This study revealed delayed neurodegeneration in the substantia nigra 8 weeks after 12.5 minutes of global ischemia in rat brain. Following neuronal loss of 30–40% in central and dorsolateral striatum at day 3, neuronal damage in the substantia nigra (SN) was assessed at 4–8 weeks using immunohistochemistry for glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), and calretinin (CR). At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)—significantly decreased. CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n = 5) to day 56 (n = 7, ANOVA, p < .01). Movement coordination was impaired at day 56, as evaluated using beam-walking test (time-to-traverse 5.6 ± 1.2 sec versus 11.8 ± 5.4 sec; sham versus ischemia, p < .05, n = 5, and 7, resp.). Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.
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