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Background: The complex interplay between ethnicity, Fitzpatrick skin type (FST), and hirsutism in patients with polycystic ovarian syndrome (PCOS) is poorly understood. Objective: In this cross-sectional, retrospective analysis, we examined the prevalence, severity, and distribution of hirsutism with clinician-rated site-specific and total modified Ferriman-Gallwey (mFG) visual scoring in a diverse cohort of American patients with PCOS. Methods: Independent analyses were conducted on the basis of patient-reported FST ratings and ethnicity. Results: In this PCOS cohort, a correlation was found between hirsutism and ethnicity and the highest prevalence of hirsutism and total mFG scores was observed in Hispanic, Middle Eastern, African American, and South Asian patients. A positive correlation between hirsutism and FST was also observed with an increasing prevalence of hirsutism in the group of patients with higher FSTs. Significant trends in the anatomic distribution of hirsutism were observed between ethnic groups as well. A higher facial mFG score was found in African American patients but higher mFG scores in the truncal and extremity regions were observed in Middle Eastern patients. Truncal hirsutism was also associated with higher FSTs. Conclusions: Ethnicity and FST may be important variables in both the quantitative and qualitative presentations of hirsutism in women with PCOS and should be considered in the diagnostic evaluation of any patient who is suspected of having the condition. Previously published studies that examined ethnicity, FST, and hirsutism in homogeneous cohorts limited comparison and generalizability but the strength of this study lies in its detailed analysis within a single large and diverse PCOS cohort. Validated studies are needed to determine whether clinical criteria for hirsutism should be adjusted for ethnicity and FST in the PCOS population and particularly within diverse cohorts and patients of mixed ancestry. Keywords: PCOS, hirsutism, ethnicity, Fitzpatrick skin type, hyperandrogenism, modified Ferriman-Gallwey

Contamination of water by heavy toxic metal ions such as (e.g., Cr 6+ , Mn 2+ , Ni 2+ , Cu 2+ , Zn 2+ , As 3+ Pb 2+ , Cd 2+ , and Ag + ) can lead to serious environmental and human health problems because of their acute and chronic toxicity to the biological system. In recent decades, research has been directed to alternative production of cheaper sustainable ecofriendly adsorbents with low carbon footprints. Moringa oleifera as an example for terrestrial plant and Eichhornia crassipes commonly known as water hyacinth (WH) as an aquatic plant, are simple effective natural and powerful adsorbents for heavy metals removal. Both plants have invasive growth tendency. They can be easily utilized in developed communities and in rural areas to produce clean water. This review is a comprehensive summary of M. oleifera (MO) and E. crassipes (WH) uses in impure water treatments with a particular attention to their role in reducing carbon footprint. PubMed, Science Direct and Springer were the search data engines that the article referred to from the years 2009-2023., Competing Interests: Declarations. Ethical Approval: This review article has not been published previously and is also not under consideration for publication elsewhere and not submitted to a preprint server prior to submission on ESPR. Consent to participate: I declare that the review article has been approved by me and co-author. Consent for publication: I declare that, if accepted, it will not be published elsewhere in the same form, in English or in any other language, without the written consent of the Publisher. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nod-like receptor pyrin domain-1 containing 3 (NLRP3) inflammasome/tumor necrosis factor alpha (TNFα)/nuclear factor kappa B (NFκB) inflammatory pathway is known to be involved in the pathogenesis of ulcerative colitis (UC). Inversely, miRNA-223 can exert counter-regulatory effect on NLRP3 expression. The mulberry tree (Morus macroura) fruit is attaining increased importance for its antioxidant and anti-inflammatory activity in addition to its high safety profile. Accordingly, we attempted to explore the possible protective effect of mulberry fruit extract (MFE) in acetic acid (AA)-induced UC rat model. Phytochemical constituents of MFE were characterized using high performance liquid chromatography coupled to mass spectrometry (HPLC-MS). In the in vivo study, three doses of MFE were orally given for seven days before intra-rectal induction of UC by AA on day eight. Screening study revealed that MFE (300 mg/kg) significantly reduced macroscopic and microscopic UC scores. Biochemically, MFE ameliorated oxidative stress, levels of TNFR1, NLRP3, p-NFκB p65, TNFα, IL-1β, and IL-18, caspase-1 activity, but enhanced miRNA-223 expression. In conclusion, our study provided a novel protective impact for MFE against UC, in which miRNA-223 and TNFα/NFκB/NLRP3 pathway are involved. These results provide a promising step that might encourage further investigations of MFE as a protective agent in UC patients., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Chronic Hepatitis C virus (HCV) infection is associated with progressive liver inflammation which in turn leads to cirrhosis and finally causes hepatocellular carcinoma (HCC). By different escape mechanisms, the virus succeeds to evade the innate and acquired immune responses to establish chronic infection., Aim: This study aimed to evaluate the level of chemokine CXCL9 and its correlation with some biochemical parameters in different subjects of HCV patients., Materials and Methods: A total of 83 persons participated in this study including healthy subjects without both HCV antibodies and HCV RNA (22.9%), HCV treated responders accomplished SVR post treatment, with HCV antibodies and absence of HCV RNA (24.1%), spontaneous or natural clearance patients, with positive HCV antibodies and negative HCV RNA without treatment (26.5%) and chronic HCV-patients, with both positive HCV antibodies and HCV RNA with no treatment (26.5%). HCV RNA was quantitated by real time PCR and serum CXCL9 level was measured by ELISA commercial kit pre-coated with human MIG/CXCL9 antibody. Assessment of biochemical and hematological parameters was carried out., Results: Data showed that, the level of CXCL9 was significantly increased in chronic individuals (627.1 pg/ml) (P< 0.001) than spontaneous clearance (107.76 pg/ml) and responder subjects (117.28 pg/ml) (P⩽ 0.05). No correlation has been found between CXCL9 level and viral load. Furthermore, CXCL9 levels correlated variably with some biochemical and hematological parameters according to each subject., Conclusion: Serum Chemokine CXCL9 level is associated with spontaneous clearance of HCV and response to HCV treatment, which may be identified as a predictive marker among HCV patients.

Rho-kinase enzymes are one of the most important targets recently identified in our bodies. Several lines of evidence indicate that these enzymes are involved in many diseases and cellular disorders. ROCK inhibitors may have clinical applications for cancer, hypertension, glaucoma, etc. Our study aims to identify the possible involvement of Rho-kinase inhibition to the multiple biological activities of adlay seeds and provide a rationale for their folkloric medicines. Hence, we evaluated Rho-kinase I and II inhibitory activity of the ethanol extract and 28 compounds derived from the seeds. A molecular docking assay was designed to estimate the binding affinity of the tested compounds with the target enzymes. The results of our study suggest a possible involvement of Rho-kinase inhibition to the multiple biological activities of the seeds. Furthermore, the results obtained with the tested compounds revealed some interesting skeletons as a scaffold for design and development of natural Rho-kinase inhibitors.

An adenine derivative, 9-β-D-glucopyranosyl adenine, reported for the first time from a natural source, in addition to nine known compounds were isolated from the seeds of Coix lacryma-jobi. Their structures were elucidated based on extensive spectroscopic and chemical studies. The isolated compounds and the ethanol extract have been assayed for melanin inhibition using B16-F10 melanoma cell line. The results of our study suggested the potential use of Coix lacryma-jobi seeds as a skin whitening agent and reveal the seeds to be a rich source of important phytochemicals with melanogenesis inhibitory activity. Among the isolated compounds, coixol (2) and 2-O-β-glucopyranosyl-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (8) exhibited potent melanogenesis inhibitory activity with no obvious melanocytotoxicity. The rest of the compounds showed weak to moderate activity.

Recent studies identified Rho-kinase enzymes (ROCK-I and ROCK-II) as important targets that are involved in a variety of diseases. Synthetic Rho-kinase inhibitors have emerged as potential therapeutic agents to treat disorders such as hypertension, stroke, cancer, diabetes, glaucoma, etc. Our study is the first to screen the total ethanol extract of the medicinal mushroom Ganoderma lingzhi with thirty-five compounds for Rho-kinase inhibitory activity. Moreover, a molecular binding experiment was designed to investigate the binding affinity of the compounds at the active sites of Rho-kinase enzymes. The structure-activity relationship analysis was investigated. Our results suggest that the traditional uses of G. lingzhi might be in part due to the ROCK-I and ROCK-II inhibitory potential of this mushroom. Structure-activity relationship studies revealed some interesting features of the lanostane triterpenes that potentiate their Rho-kinase inhibition. These findings would be helpful for further studies on the design of Rho-kinase inhibitors from natural sources and open the door for contributions from other researchers for optimizing the development of natural Rho-kinase inhibitors.

A new oxygenated lanostane-type triterpene, named lucidumol C, together with six known compounds, was isolated from the chloroform extract of the fruiting bodies of Ganoderma lingzhi. Structures were established based on extensive spectroscopic and chemical studies. Potential cytotoxic activities of the isolated compounds were evaluated against human colorectal carcinoma (HCT-116, Caco-2), human liver carcinoma (HepG2), and human cervical carcinoma (HeLa) cell lines using WST-1 reagent. Selectivity was evaluated using normal human fibroblast cells (TIG-1 and HF19). Among the compounds, lucidumol C showed potent selective cytotoxicity against HCT-116 cells with an IC50 value of 7.86 ± 4.56 µM and selectivity index (SI) >10 with remarkable cytotoxic activities against Caco-2, HepG2 and HeLa cell lines.

The essential oil from the aerial parts of Nephrolepis exaltata and Nephrolepis cordifolia obtained by hydro-distillation were analyzed by gas chromatography/ mass spectrometry. The essential oils exhibited potential antibacterial and antifungal activities against a majority of the selected microorganisms. NEA oil showed promising cytotoxicity in breast, colon and lung carcinoma cells. The results presented indicate that NEA oil could be useful alternative for the treatment of dermatophytosis. Comparative investigation of hydro-distilled volatile constituents from aerial parts (A) of Nephrolepis exaltata (NE) and Nephrolepis cordifolia (NC) (Family Nephrolepidaceae) was carried out. Gas chromatography/mass spectrometry revealed that oils differ in composition and percentages of components. Oxygenated compounds were dominant in NEA and NCA. 2,4-Hexadien-1-ol (16.1%), nonanal (14.4%), β-Ionone (6.7%) and thymol (2.7%) were predominant in NEA. β-Ionone (8.0%), eugenol (7.2%) and anethol (4.6%) were the main constituents in NCA. Volatile samples were screened for their antibacterial and antifungal activities using agar diffusion method and minimum inhibitory concentrations. The cytotoxic activity was evaluated using viability assay in breast (MCF-7), colon (HCT-116) and lung carcinoma (A-549) cells by the MTT assay. The results revealed that NEA oil exhibited potential antimicrobial activity against most of the tested organisms and showed promising cytotoxicity.

Co(II), Ni(II), Cu(II) and Pd(II) complexes of 4-amino-5-pyrimidinecarbonitrile (APC) have been synthesized and characterized using elemental analysis, magnetic susceptibility, mass spectrometry, infrared (4000-200 cm(-1)), UV-Visible (200-1100 nm), (1)H NMR and ESR spectroscopy as well as TGA analysis. The molar conductance measurements in DMSO imply non-electrolytic complexes, formulated as [M(APC)2Cl2] where M=Co(II), Ni(II), Cu(II) and Pd(II). The infrared spectra of Co(II), Ni(II) and Cu(II) complexes indicate a bidentate type of bonding for APC through the exocyclic amino and adjacent pyrimidine nitrogen as donors whereas APC coordinated to Pd(II) ion as a monodentated ligand via a pyrimidine nitrogen donor. The magnetic measurements and the electronic absorption spectra support distorted octahedral geometries for Co(II), Ni(II) and Cu(II) complexes however a square planar complex was favored for the Pd(II) complex (C2h skeleton symmetry). In addition, we carried out B3LYP and ω-B97XD geometry optimization at 6-31G(d) basis set except for Pd(II) where we implemented LanL2DZ/6-31G(d) combined basis set. The computational results favor all trans geometrical isomers where amino N, pyrimidine N and Cl are trans to each other (structure 1). Finally, APC and its divalent metal ion complexes were screened for their antibacterial activity, and the synthesized complexes were found to be more potent antimicrobial agents than APC against one or more microbial species., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A new acylated kaempferol glycoside, kaempferol 3-O-α-l-rhamnopyranosyl-(1 → 6)-O-[β-d-glucopyranosyl-(1 → 2)-4-O-acetyl-α-l-rhamnopyranosyl-(1 → 2)]-β-d-galactopyranoside, has been isolated from the leaves of Tipuana tipu (Benth.) Lillo growing in Egypt, along with three known flavonol glycosides, kaempferol 3-O-rutinoside, quercetin 3-O-rutinoside (rutin) and kaempferol 3-O-[α-l-rhamnopyranosyl-(1 → 6)]-[α-l-rhamnopyranosyl-(1 → 2]-β-d-glucopyranoside. Structure elucidation was achieved through different spectroscopic methods. Structure relationship with anti-inflammatory activity using carrageenin-induced rat paw oedema model is discussed.

Machaerium, in the family Fabaceae, predominantly is a genus of a Neotropical distribution of trees, shrubs, and lianas occurring from southern Mexico to Brazil and northern Argentina and as far as South America. Several Machaerium species are widely used in traditional medicine and are considered to have multiple medicinal properties. This review aims to provide up-to-date and comprehensive information on the taxonomy, phytochemistry, traditional uses and biological activities of plants in the genus Machaerium.

Background: Hepatitis C virus (HCV) is associated with fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and end-stage liver disease. In the normal liver, fibronectin plays crucial roles in various cellular functions, including cell adhesion, migration, proliferation, and differentiation. Increased expression of fibronectin is associated with areas of physiological or pathological tissue remodeling, including wound healing and tissue repair. The aim of the current study was to correlate the cellular fibronectin expression level in peripheral blood fibrocytes of chronic HCV patients with the severity of liver fibrosis as detected by liver biopsy., Methods: The present study was conducted on 20 fibrotic liver cases with detectable HCV RNA, 10 HCV cirrhotic liver cases, and 10 control subjects of matched age and sex. Cellular fibronectin RNA was detected by PCR., Results: The mean level of cellular fibronectin expression in cases with liver fibrosis was significantly higher than the corresponding level in cases with liver cirrhosis (p = 0.019). Control individuals did not express cellular fibronectin. There was also a significant correlation between the Metavir score and cellular fibronectin RNA, APRI, and FIB-4 scores. However, based on the area under the curve (AUC) values, cellular fibronectin showed a lower diagnostic performance than APRI and FIB-4 scores., Conclusions: Cellular fibronectin RNA showed satisfactory reproducibility and could be used to differentiate HCV fibrotic liver (F1-F3) and HCV cirrhotic liver (F4) from normal liver (F0).

The new acetylated kaempferol tetraglycoside, kaempferol-3-O-[2″(4-acetylrhamnopyranosyl)-3″-galactopyranosyl] robinobioside (1), was isolated from the aqueous methanolic leaf extract of Tipuana tipu Benth. The known kaempferol 3-[2″-(4-acetyl-rhamnosyl)] robinobioside (2), kaempferol 3-O-2″-rhamnopyranosylrutinoside (3), rutin (4), kaempferol 3-O-rutinoside (5), kaempferol 3-O-glucopyranoside (6), kaempferol 3-O-galactopyranoside (7), quarcetin 3-O-glucopyranoside (8), kaempferol (9) and quercetin (10) together with the chlorogenic acid (11) were also isolated and characterised. Structures were established on the basis of chemical and spectroscopic analysis including (1)H NMR, (13)C NMR, 2D NMR and ESI-MS. The methanol extract exhibited moderate antioxidant activity, IC50 28.96 μg/mL, compared with ascorbic acid (1.83 μg/mL) and tertiary-butylhydroquinone (1.92 μg/mL). The methanol and chloroform extracts exhibited potent cytotoxic activity; the former was found to be active against larynx and liver cell lines, while the latter being active against intestine and liver cell lines.

The infrared (4000-200 cm(-1)) spectrum for 4-amino-5-pyrimidinecarbonitrile (APC, C5H4N4) was acquired in the solid phase. In addition, the (1)H and (13)C NMR spectra of APC were obtained in DMSO-d6 along with its mass spectrum. Initially, six isomers were hypothesized and then investigated by means of DFT/B3LYP and MP2(full) quantum mechanical calculations using a 6-31G(d) basis set. Moreover, the (1)H and (13)C NMR chemical shifts were predicted using a GIAO approximation at the 6-311+G(d,p) basis set and the B3LYP method with (and without) solvent effects using PCM method. The correlation coefficients showed good agreement between the experimental/theoretical chemical shift values of amino tautomers (1 and 2) rather than the eliminated imino tautomers (3-6), in agreement with the current quantum mechanical calculations. Structures 3-6 are less stable than the amino tautomers (1 and 2) by about 5206-8673 cm(-1) (62.3-103.7 kJ/mol). The MP2(full)/6-31G(d) computational results favor the amino structure 1 with a pyramidal NH2 moiety and calculated real vibrational frequencies, however; structure 2 is considered a transition state owing to the calculated imaginary frequency. It is worth mentioning that, the calculated structural parameters suggest a strong conjugation between the amino nitrogen and pyrimidine ring. Aided by frequency calculations, normal coordinate analysis, force constants and potential energy distributions (PEDs), a complete vibrational assignment for the observed bands is proposed herein. Finally, NH2 internal rotation barriers for the stable non-planar isomer (1) were carried out using MP2(full)/6-31G(d) optimized structural parameters. Our results are discussed herein and compared to structural parameters for similar molecules whenever appropriate., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Two new flavonol glycosides, isorhamnetin 3-O-β-glucopyranoside-4'-O-β-xylopyranoside (1) and kaempferol 3-O-β-glucopyranoside -4'-O-β-xylopyranoside (2), were isolated from the defatted aqueous methanol extract of the whole plant Diplotaxis harra along with 12 known flavonols (3-14). They were characterised by chemical and spectral methods. The 70% aqueous methanol, chloroform and defatted aqueous methanol plant extracts exhibited significant antioxidant effects (nitroblue tetrazolium reduction method). Their cytotoxic activity was carried out against 11 tumour cell lines (sulphorhodamine B assay). The three extracts expressed the greatest antiproliferative activity against colon 38, P388 and MKN-28 with GI50 (0.45, 0.4, 0.07 μg/mL) and against P388 [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay] with IC50 (0.26, 0.24, 0.25 μg/mL), respectively. The chloroform extract showed the highest activity as eukaryotic DNA topoisomerase II inhibitors of P388 with IC50 0.24 μg/mL. Antiviral screening of the extracts and the pure compounds against foot-and-mouth disease virus types A and O revealed a prominent inhibition of its cytopathic effect.

A precise and specific 1H-NMR method has been developed for the assay of papaverine hydrochloride (1) as a bulk drug, as well as in tablet and injection dosage forms. The assay depends upon the integration of the 12 protons of the four methoxy groups of 1 relative to that of the three methyl protons of acetanilide (internal standard). In addition to the accurate quantitative determination of 1, the method provides a specific means of identifying 1 as well as detecting other alkaloids or impurities.

A new iridoid gentiobioside (4, assigned the name phlomiside) was isolated from the leaves of Phlomis aurea growing in Egypt, in addition to auroside (1), lamiide (2), 8-epi-loganin (3), forsythoside B (5), quercetin-3-O-beta-D-glucopyranoside (6) and kaempferol-3-O-beta-D-glucopyranosyl-(1-6)-beta-D-glucopyranoside (7). Structures of these compounds were elucidated by conventional methods of analysis as well as by different spectroscopic techniques.

Three acylated flavonol diglucosides, kaempferol 3-O-beta-(6"-O-E-p-coumaroylglucoside)-7-O-beta-glucoside; quercetin 3-O-beta-(6"-O-E-p-coumaroylglucoside)-7-O-beta-glucoside; isorhamnetin 3-O-beta-(6"-O-E-p-coumaroylglucoside)-7-O-beta-glucoside were isolated from the whole plant aqueous alcohol extract of Lotus polyphyllos. The known 3,7-di-O-glucosides of the aglycones kaempferol, quercetin and isorhamnetin were also characterized. All structures were established on the basis of chemical and spectral evidence.

A new phenylpropanoid glycoside, crenatoside, as well as the known phenylpropanoid, acteoside, have been isolated from the aerial parts of Orobanche crenata. Their structures have been determined by spectroscopic methods as well as by means of chemical evidence.

A-3665 is a new short-acting synthetic opioid of the piperidine class. We conducted a double-blind, escalating dose comparison of A-3665 to alfentanil and placebo. Analgesic efficacy was assessed after the administration of A-3665 in increasing intravenous doses (0.25, 0.5, 1, 2, 4, 8, 16, 32, and 64 micrograms/kg) to nine groups of volunteers. At the lower doses (0.25, 0.5, 1, and 2 micrograms/kg), five volunteers were in each group; four received A-3665 and one received placebo in a double-blind manner. There were nine volunteers in each of the next three groups; four received A-3665 (4, 8, or 16 micrograms/kg), four received alfentanil (4, 8, or 16 micrograms/kg), and one received placebo. At the 32 micrograms/kg and 64 micrograms/kg dose levels, five subjects each were to be enrolled (four to receive A-3665 and one to receive placebo); however, the study was terminated after two subjects in the 64 micrograms/kg group had significant respiratory depression. Both drugs caused potent analgesia, compared with placebo, with peak effect occurring 3 min after injection. There was no significant difference in analgesic potency of A-3665 and alfentanil as measured by tolerance to tibial pressure at 3 min. At the dose of 16 micrograms/kg, both drugs significantly increased pain tolerance to tibial pressure compared with placebo at 3 min, but alfentanil continued to display significant analgesic effect versus placebo and versus A-3665 at 6, 11, and 15 min after injection. A-3665 caused significant respiratory depression at doses of 32 micrograms/kg and 64 micrograms/kg, but alfentanil did not induce significant respiratory depression at the doses tested.(ABSTRACT TRUNCATED AT 250 WORDS)

A new phenylpropanoid glycoside, 2'-O-acetylpoliumoside, as well as two known compounds--acteoside and 2'-O-acetylacteoside--have been isolated from the aerial parts of Orobanche ramosa. The structures have been elucidated by spectroscopic methods and supported by chemical evidences.

The conversion of zearalenone by various microorganisms was studied. A new polar metabolite was formed in addition to alpha- and beta-zearalenols. The structure of the new metabolite was determined as zearalenone-4-O-sulfate conjugate on the basis of enzymatic and acid hydrolysis, followed by mass spectrometry, nuclear magnetic resonance, and infrared spectroscopic analysis. The results obtained demonstrate that Rhizopus arrhizus catalyzes sulfation of zearalenone at the C-4 hydroxyl group.

Pentamorphone is a novel, potent opiate with rapid onset and short duration of action that has been reported to produce analgesia with limited depression of ventilation. We quantified the effects of pentamorphone (0.08, 0.24, and 0.60 micrograms/kg, IV) on ventilatory responses to hypercapnia and hypoxia in 12 healthy volunteers. Normoxic hypercapnia and isocapnic hypoxia were induced through a rebreathing method. During each test we recorded ventilation (VE), end tidal carbon dioxide tension (PETCO2), and arterial oxygen saturation (SO2) using a pulse oximeter. Using linear regression analysis of the relationships between VE and PCO2 during hypercapnia and VE and SO2 during hypoxia, we determined the slope (slope CO2) and intercept (V55), both at PCO2 55 mm Hg, and the slope (slope O2) and intercept (V80) at SO2 80%. Pentamorphone produced dose-related reductions in the ventilatory responses to both hypercapnia and hypoxia. Maximal depression occurred 15 min after injection of pentamorphone with all doses; the highest dose (0.60 micrograms/kg) produced 48% and 53% reductions in slope CO2 and V55, and 42% and 22% reductions in slope O2 and V80, respectively, relative to parallel saline controls. The respiratory depressant actions of pentamorphone were short-lived, as all parameters returned to baseline levels within 45 min. Testing was continued for 180 min after injection, but no delayed ventilatory effects were detected, and minimal side effects were reported, even at the highest dose. The findings confirm previous reports that pentamorphone has limited ventilatory depressant effects in humans in doses that (in other studies) have been associated with clinically effective analgesia.

Cerebrocortical oxygenation was monitored in 8 healthy adults during exposure to sustained isocapnic hypoxia. Subjects were maintained at an arterial oxygen saturation (SaO2) of 80% for 12 min with a rebreathing circuit while cerebrocortical oxygenation was assessed non-invasively using near-infrared (NIR) spectroscopy to measure changes in the oxidation state of cytochrome a,a3 (Cyt a,a3) and changes in cortical blood volume (tBV). During sustained hypoxia, subjects demonstrated a biphasic ventilatory response. The mean minute ventilation (VE) peak response was 255% of baseline at an average of 3.4 +/- 0.5 min (mean +/- SE) after the initiation of hypoxia. A subsequent significant attenuation of VE to 163% (P less than 0.05) of baseline occurred after an additional 8.6 min. NIR monitoring revealed a significant (P less than 0.05) decrease in oxidized Cyt a,a3 as well as a significant (P less than 0.05) increase in tissue blood volume (tBV) at the time of peak VE. Both Cyt a,a3 and tBV remained stable during the remainder of the hypoxic period, despite attenuation of VE during sustained hypoxia. The data suggest that cerebrocortical oxygenation and blood flow remain constant when the ventilatory attenuation is observed during sustained hypoxia.

We have developed a series of sandwich ELISA for the quantitation of kidney derived urinary antigens (UA) utilizing monoclonal antibodies specific for antigens localized in cells of defined subunits of the nephron of human kidney. Antigens derived from the distal and proximal parts of the tubular system as well as antigens localized over its entire length can be detected and quantified in urine samples. Antigen excretion was measured in the urine of healthy individuals, patients with various diseases with and without kidney involvement, kidney transplant recipients, and healthy volunteers after receiving antibiotics. Low antigen excretion values were found in healthy individuals, patients with diseases primarily affecting the glomerulus, and inactive phases of chronic diseases. Toxic side effects of drugs were reflected by slightly (antibiotic drugs) or strongly (cytostatic drugs) enhanced antigenuria. Excretion of some or all of the antigens was always indicative of massive alteration of tubular structures, such as in acute phases of tubulointerstitial disease or during rejection episodes in kidney transplant recipients. The results obtained indicate that it is possible to obtain information on the location and extent of acute primary processes in the kidney with these tests.

Mice were irradiated and infused with BALB/c Friend virus-induced FLD-3 erythroleukemia cells. Growth of the cells was estimated by measuring splenic incorporation of 5-iodo-2'-deoxyuridine-125I 5 days after cell transfer. BALB/cJ and C3H mice were 'poor responders' in that FLD-3 cells grew well in their spleens, while mice of other strains were 'good responders', resisting the growth of FLD-3 cells. No H-2 or Fv genetic locus was associated with resistance. Athymic nude mice and mice depleted of marrow tissue by 89Sr or estradiol resisted FLD-3 cells, indicating that the effectors were thymus- and marrow-independent. Silica, carrageenan and Propionibacterium acnes organisms all altered resistance, suggesting a function of macrophages. Neither interferon nor anti-interferon serum treatment altered resistance. Anti-asialo GM1 serum inhibited resistance to FLD-3 cells in vivo and inhibited natural cytotoxic (NC) activity against FLD-3 cells in vitro. NC (FLD-3) activity was greatly decreased in spleens 3 days after irradiation, in contrast with NK (YAC-1) and NC(WEHI-164.1) activities. Moreover, a 3-day delay in infusion of FLD-3 cells 'synergized' with silica in weakening genetic resistance in vivo. Thus, natural immunity to FLD-3 cells in vivo differs from that of genetic resistance to normal bone marrow cell allografts, and the lysis of FLD-3 cells in vitro seems to be mediated by cells which do not easily fit into the definition of natural killer (NK) or natural cytotoxic (NC) cells.

Lethally irradiated mice were infused with syngeneic, H-2 allogeneic, parental strain, or H-2 heterozygous bone marrow cells. They were injected daily with rabbit anti-mouse interferons (IFN)-alpha/beta or gamma or with IFN-alpha/beta. The growth of donor-derived cells was judged 5 days later by measuring splenic incorporation of 5-iodo-2'-deoxyuridine-125I into DNA. Antibodies to IFN-alpha/beta, but not to IFN-gamma, weakened genetic (both hybrid and allogeneic) resistance to marrow cell grafts. IFN-alpha/beta stimulated hybrid and allogeneic resistance, the latter even in genetically "poor responder" mice. Mice pretreated with silica, which weakens genetic resistance, were stimulated by IFN-alpha/beta to resist incompatible marrow cell grafts; however, IFN-alpha/beta failed to reverse the effects of antiasialo GM1 serum on marrow graft rejection. IFN-alpha/beta did not inhibit the growth of syngeneic marrow cells and did not stimulate resistance to H-2 heterozygous bone marrow cells. We propose that genetic resistance occurs in two discrete steps. In the first step, hemopoietic histocompatibility (Hh) antigens are recognized by one host cell type, and this recognition leads to IFN-alpha/beta secretion by a silica-sensitive cell. In the second step, asialo GM1-positive natural killer cells stimulated by IFN-alpha/beta recognize Hh antigens on marrow stem cells and cause rejection. The defects in resistance observed in genetically poor responder mice and in mice treated with silica appear to involve the first step in recognition. The lack of rejection of H-2 heterozygous (Hh-) marrow cells by parental strain mice injected with IFN-alpha/beta indicated that specific Hh recognition is critical in the second step of genetic resistance.