Augmentation Response Research Articles

Determining the augmentation ratio and response behaviour of a Diffuser Augmented Wind Turbine (DAWT)

An experimental study was performed on a full-scale DAWT to understand its response behaviour to changes in wind speed fluctuations. A novel diffuser was designed from the results of previous numerical studies and was manufactured using lightweight materials. The resultant DAWT was made portable and tested in three wind directions. Wind speeds, wind directions and output power was recorded from both the bare wind turbine i.e. before it was applied with the diffuser and then the resultant DAWT. From experimental testing of the DAWT, wind speeds to the rotor were increased by 136% from 1.02 m/s to 2.41 m/s. The augmentation ratio was evaluated at 8.32 and the DAWT exhibited better responsive behaviour than the bare wind turbine in terms of matching the expected output power profile and a smaller response time.

Augmentation effect of ketamine by guanosine in the novelty-suppressed feeding test is dependent on mTOR signaling pathway

The ketamine's potential for the treatment of refractory depression and anxiety has been considered one the most important discoveries in the last years, however, repeated use of ketamine is limited due to its side/adverse effects. Therefore, the search for effective augmentation strategies that may reduce ketamine doses is welcome. Therefore, this study sought to augment the effect of ketamine by guanosine in the novelty-suppressed feeding (NSF) test, a behavioral paradigm able to detect depression/anxiety-related behavior. Acute administration of guanosine (0.05 mg/kg, p.o.), similar to ketamine (1 mg/kg, i.p.), produced a rapid behavioral response in mice submitted to NSF test. Moreover, the coadministration of sub-effective doses of guanosine (0.01 mg/kg, p.o.) and ketamine (0.1 mg/kg, i.p.) was effective in mice submitted to NSF test. Subsequently, the intracellular mechanism underpinning the augmentation effect of ketamine by guanosine was investigated. Our results suggest that augmentation response of ketamine by guanosine in the NSF test probably involves the activation of mTOR signaling, since the treatment with rapamycin (0.2 nmol/site, i.c.v., a selective mTOR inhibitor) completely abolished this effect. This augmentation strategy also increased mTOR phosphorylation (Ser2448) in the hippocampus, reinforcing the role of mTOR in this augmentation response. However, no changes in the p70S6K, PSD-95, GluA1, and synapsin immunocontents were found in the hippocampus of ketamine plus guanosine-treated mice. Overall, results provide evidence that guanosine is able to augment the effect of ketamine in the NSF test via mTOR activation, a finding that might have therapeutic implications for the management of depression/anxiety.

A Burn Progressive Care Unit: Customized Care from Admission Through Discharge

Four East is a 24-bed burn progressive care unit (BPCU) located in the burn center of the Institute of Surgical Research, San Antonio Military Medical Center, Fort Sam Houston, Texas. Patients in the BPCU are transferred from the burn ICU (intensive care unit, BICU), admitted through the emergency department or the burn clinic, or are readmissions for surgical scar revisions. BPCU patients may arrive accompanied by the burn center’s dedicated burn flight team, or SMART team (special medical augmentation response team), or with civilian personnel as transfers from other area hospitals. Criteria for direct admission to the BPCU are total body surface area (TBSA) burn of less than 20% with stable vital signs and lab values and minimal oxygen requirements.

Combination immunotherapy of MAb B6.1 with fluconazole augments therapeutic effect to disseminated candidiasis

We recently reported that IgM MAb B6.1, specific for β-1, 2-mannotriose on the cell wall of Candida albicans, is therapeutic to disseminated candidiasis due to C. albicans. In the current study, we examined if MAbB6.1 enhances therapeutic effect of fluconazole (FLC) to the disseminated disease. To assess the combination effect, determination by the kidneys-colony forming unit and survival times were used. Results showed that the therapeutic effect of FLC on mice with disseminated candidiasis was dose-dependent, but a FLC dose at 0.8 mg/kg body weight of mice was ineffective. To determine combination effect, mice treated intraperitoneally with a combination of FLC plus MAb B6.1 at 1 h post-infection - a condition of developing partial therapeutic activity - enhanced survival times beyond the effect by only antibody (p < 0.05). The resulting MST (mean survival times) value from the combination-received mice was almost the same as MST value from 3.2 mg FLC dose-given animals (p < 0.05). Another combination of 1.6 mg FLC dose and B6.1 reduced severity of the disseminated disease at almost the same rate as combination efficacy of 0.8 mg FLC dose plus B6.1. This data indicates that B6.1 acts in concert with FLC and that this combination therapy augments protection, which suggests a possibility of reducing FLC dose. The augmentation response was specific because an irrelevant IgM MAb S9 was not effective to the disseminated disease. Thus, our present studies demonstrate that this combination immunotherapy may be a way of solving the problem of limited antifungal drug choices caused by drug-resistant C. albicans.

Femoropopliteal prosthetic bypass graft infection due to Mycobacterium abscessus localized by FDG-PET/CT scan

A patient with postvascular graft placement presented with bacteremia but no localizing symptoms. Our standard infected graft workup of computed tomography (CT) scan, ultrasound scan, magnetic resonance imaging (MRI) scan, and additional laboratory tests did not localize the infection source. Nuclear medicine had three options including white blood cell (WBC) scan, gallium scan, and the fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT scan. FDG-PET/CT imaging alone demonstrated the location. We present an unusual case of Mycobacterium abscessus in a vascular graft not localized with CT scan, ultrasound scan, or MRI scan and could only be localized with FDG-PET/CT scan.

Ultrasonography for suspected deep vein thrombosis: how useful is single-point augmentation?

To assess the role of single-point augmentation of spectral Doppler flow in the diagnosis of acute deep vein thrombosis (DVT). Secondary objectives included identifying the augmentation response in non-DVT diagnoses. Patients attending the ultrasound departments of two hospitals for investigation of suspected acute DVT during an 8-month period were recruited to the study group. Spectral Doppler assessment of the superficial femoral vein was recorded during Valsalva and calf compression manoeuvres in the asymptomatic and symptomatic legs. The Doppler waveforms from the symptomatic limb were characterized as "normal" or "abnormal" by the operator. Standard compression ultrasonography of the symptomatic leg was then performed with the presence of DVT or an alternative diagnosis documented. One hundred and sixty-seven patients underwent ultrasound examinations using the study methodology. Nine patients were subsequently excluded due to bilateral DVT or inability to tolerate calf compression. The mean age of the remaining 158 patients was 65.4 years with 28 DVTs identified (18% of patients). Calf compression elicited a normal response in 118/130 of non-DVT examinations (specificity 91%) and an abnormal response in 18/28 DVT examinations (sensitivity 64%). Diminished or absent augmentation was identified in alternative diagnoses that included haematoma and Baker's cyst. This study demonstrates that single-point augmentation has a low sensitivity in suspected lower-limb DVT, and that the majority of undetected DVTs are isolated to the calf veins. An abnormal augmentation response is a poor predictor of lower-limb DVT as alternative diagnoses can produce diminished or reduced augmentation. Therefore, single-point augmentation does not add to the standard compression ultrasound examination for suspected DVT and should not be routinely performed.

Ultrasonography for DVT – how useful is single point augmentation?

Aims: It is unclear whether the absence of normal augmentation of spectral Doppler flow at a single point is an accurate predictor of lower limb acute deep vein thrombosis (DVT) or whether its presence reliably excludes DVT. Our main objective was to assess the role of single point augmentation of spectral Doppler flow in the diagnosis of acute DVT. Secondary objectives included identifying the augmentation response in non-DVT diagnoses. Methods: Patients attending the ultrasound department of two hospitals during an eight-month period for investigation of suspected acute DVT were eligible. Spectral Doppler assessment of the superficial femoral vein was recorded during valsalva manoeuvre and calf compression in the asymptomatic and symptomatic legs. The Doppler waveform was characterised as 'Normal' or 'Abnormal'. Standard compression ultrasonography of the symptomatic leg was then performed with the presence of DVT or an alternative diagnosis documented. Results: 167 patients underwent ultrasound examination using the study methodology. 9 patients were subsequently excluded due to bilateral DVT or inability to tolerate calf compression. The remaining 158 patients demonstrated a mean age of 65.4 years with 28 DVTs identified (17.7% of patients). Calf compression elicited a normal response in 118/130 non DVT examinations (specificity=90.8%) and was abnormal in 18/28 DVT examinations (sensitivity=64.3%). Diminished or absent augmentation was identified in alternative diagnoses that included haematoma and Baker's cyst. Conclusions: This study demonstrates that single point augmentation of venous flow has a high specificity and negative predictive value in the assessment of suspected acute DVT. However, the sensitivity is low with 35.4% of DVTs associated with normal Doppler spectra on calf compression (the majority of these missed DVTs are isolated to the calf veins). Conversely, an abnormal augmentation response may be seen in non DVT diagnoses.

Mood stabilizer augmentation in apparently “unipolar” MDD: predictors of response in the naturalistic French national EPIDEP study

Background: Mood stabilizers (MS), especially Lithium, are used in augmentation strategies for resistant depression. However the broader bipolar spectrum (depressions with brief [i.e. 2 days] hypomania, cyclothymic and hyperthymic temperaments) has rarely been explored in such strategies. The aim of the current report is to search for predictive factors for response to mood stabilizers when used as augmentation therapy after excluding clear-cut hypomania and focusing on DSM-IV major depressive disorder (UP-MDD), which is best designated as apparently “unipolar”. Method: From the total sample of 452 major depressives (MDE) included in the French National study EPIDEP, 256 were classified as UP-MDD after eliminating DSM-IV bipolar II (≥4 days of hypomania); conservatively, we also excluded MDD with hypomania associated with antidepressants. Lifetime treatment history of UP-MDD revealed that 59 (23.3%) had received at least one MS (lithium, valpromide [French variant of divalproex], and carbamazepine) in the past; from this sub-population, 18 were considered retrospectively as good responders (30%, GR) versus 41 poor responders (70%, PR) to MS augmentation on the basis of the clinical judgment of the treating psychiatrist. Results: Comparative analyses between patients who received MS and those who did not, revealed the former group as having higher levels on the hypomania checklist and cyclothymic and depressive temperaments. The delay to MS installation was significantly longer in the PR versus GR. The profile of GR could be described as follows: younger current age, higher education; symptom-free interval between major episodes; and fewer prior depressive episodes and hospitalizations; and higher rate of MS prescription. However, no significant differences were obtained from hypomania assessment and affective temperament ratings (cyclothymic, hyperthymic, depressive). During the index (most recent) depressive episode, we obtained a significantly higher rating of “suicidal thoughts” associated with higher levels of “sadness–guilt,” psychomotor agitation, and lower “retardation–fatigue” (all from the HAM-D) in the PR group; better and faster response to current treatment (as prospectively assessed) were also observed in the GR. At this time, overall severity of depression was not linked to the quality of response to the MS. Limitations and conclusion: Despite its retrospective design, these analyses have important implications in the management of difficult or resistant “unipolar” depression by using MSs as augmentation strategy. Clinicians appeared to have used “subtle” hypomanic and cyclothymic features as a justification for augmentation. However, these features per se were not predictive of response to such augmentation. Instead, the profile of augmentation response to failed antidepressants appears to be an “activated depression” (significantly less retardation and withdrawal and higher agitation associated with greater intensity of painful and guilt-ridden sadness with suicidality), and the significantly higher rate of and earlier prescription of MSs in the course of recurrent MDD. These data suggest that resistant depressives should not stay on antidepressant or antidepressant combination for too long; MS augmentation must be instituted without much delay.

Association between response to lithium augmentation and the combined DEX/CRH test in major depressive disorder

Although lithium augmentation is the foremost and most well-documented treatment strategy for treatment resistant depression, knowledge of factors related to response remains scanty. Findings with the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) test are associated with response to treatment with a tricyclic antidepressant. This study investigated the potential predictive value of the DEX/CRH test for lithium augmentation response in major depressive disorder. The DEX/CRH test was conducted prior to lithium augmentation in 30 patients with a major depressive episode who had not responded to an antidepressant monotherapy trial of at least 4 weeks. Response status was assessed weekly using the Hamilton Rating Scale for Depression. For multivariate prediction, a logistic regression analysis was performed. Eleven (37%) patients responded to lithium augmentation within 4 weeks. Responders showed higher ACTH response and lower cortisol response in the DEX/CRH test, but results were not statistically significant. However, non-responders had a statistically significant higher cortisol/ACTH peak ratio (3.43±1.75) compared to responders (2.18±1.38) ( P=0.027). This ratio is an indicator for the sensitivity of the adrenal cortex to ACTH. A cortisol/ACTH peak ratio of 1.8 was identified as the best cutoff point to differentiate responders from non-responders. In conclusion, results suggest a more sensitive adrenal cortex in non-responders to lithium augmentation. The findings would be in line with the assumption of a more chronic course of depression with more pronounced biological alterations in the non-responder group, because chronic depression is known to cause enlargement of the adrenal gland with a subsequent hypersensitivity to ACTH. Results of this study should be confirmed in a larger study group.

Expression of adenylyl cyclase isoforms in neutrophils

In the present study, we have identified the expression of adenylyl cyclase (AC) isoforms in rat neutrophils according to the mRNA analysis and the distinct mode of regulation of isoform activity. Agarose gel electrophoresis of reverse transcription-polymerase chain reaction (RT-PCR)-amplified products resulted in a single band of the expected size for each product with nucleotide sequences corresponding to AC1 to AC9. AC1 was abundant, while AC2, 6 and 9 were of moderate expression among the AC isoforms in neutrophils based on the quantitative real-time RT-PCR analysis. Exposure of neutrophils to Ca 2+ ionophore A23187, isoproterenol and forskolin stimulated cellular cyclic AMP accumulation. EDTA and the calmodulin (CaM) antagonist, trifluoperazine, prevented the A23187-induced response. Pretreatment with pertussis toxin (PTX) inhibited the α 2-adrenergic agonist, UK14304-induced cellular cyclic AMP elevation. In addition, UK14304 augmented the cyclic AMP elevation when cells were stimulated by isoproterenol. Phorbol 12-myristate 13-acetate (PMA) attenuated the augmentation response of UK14304 and isoproterenol. Treatment of the membrane preparations from rat neutrophils with Ca 2+/CaM, forskolin, isoproterenol, GTPγS or Gβγ all increased cyclic AMP production. The addition of protein kinase C (PKC) catalytic fragment and Gβγ augmented the Ca 2+/CaM- and isoproterenol-stimulated AC activity, respectively. However, forskolin and the activated protein kinase A (PKA) attenuated the GTPγS- and isoproterenol-stimulated AC activity, respectively. KT5720, a PKA inhibitor, reversed the inhibition by PKA. Taken together, these data suggest the presence of four groups of AC isoforms in rat neutrophils.

Relationship between antidepressant partial and nonresponse and subsequent response to antidepressant augmentation

Objective: To evaluate the relationship between the degree of antidepressant nonresponse and subsequent response to lithium and triiodothyronine (T3) augmentation. Method: This is a retrospective analysis of data combined from two previous controlled studies of lithium and triiodothyronine augmentation of tricyclic antidepressants. Results: There was no difference in the rate of augmentation response between partial and nonresponders to tricyclic antidepressant treatment. Conclusions: Augmentation response does not appear to be related to the degree of nonresponse to the preceding antidepressant trial.

5-CT or DOI augments TRH analog-induced gastric acid secretion at the dorsal vagal complex.

Serotonin (5-HT) interacts with thyrotropin-releasing hormone (TRH) at the dorsal vagal complex (DVC) to augment TRH-induced stimulation of gastric acid secretion. To investigate the 5-HT receptor family involved in the augmentation response, prototypical 5-HT receptor-selective agonists (146 pmol) were coinjected with the TRH analog RX-77368 (RX; 12 pmol) into the rat DVC in a 30-nl volume. The DVC coordinates were 0.2 mm anterior, 0.2 mm right, 0.6 mm ventral with respect to the calamus scriptorius. Coinjection of RX with the 5-HT agonists 5-carboxyamidotryptamine (5-CT) or (+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI; 5-HT2 agonist) produced a 183 or 103% increase in gastric acid output compared with the RX injection alone. In contrast, coinjection of 2-methyl-5-HT (5-HT3 agonist) with RX produced no effect on RX-induced increase in gastric acid secretion. Moreover, coinjection of SC-53116 (5-HT4 agonist) decreased the gastric acid output by 45% compared with the RX response itself. Examination of the RX/5-HT agonist coinjection response in more rostral regions of the DVC using the same doses (5-CT/RX or DOI/RX) revealed that only 5-CT was effective in producing the augmented response to TRH analog. The results suggest that activation of 5-CT- or DOI-sensitive receptors augments, and of 5-HT4 receptors inhibits, the gastric acid response to TRH analog injected into the DVC. Thus the integrated response to several serotonin receptor subtypes may mediate changes to the TRH response induced by 5-HT at the DVC.

A transduction pathway associated with receptors coupled to the inhibitory guanine nucleotide binding protein Gi that amplifies ATP-mediated arachidonic acid release.

ATP is copackaged and coreleased with adrenergic, serotonergic, and cholinergic neurotransmitters, suggesting a possible interaction between the signaling pathways for ATP and these coreleased neurotransmitters. Muscarinic m2 and m4, alpha 2-adrenergic, and D2-dopaminergic neurotransmitter receptors, which have in common their ability to inhibit adenylate cyclase through the inhibitory guanine nucleotide binding protein Gi, were transfected and expressed in Chinese hamster ovary (CHO) cells that contain endogenous ATP receptors coupled to the release of arachidonic acid. Normal functional coupling of m2, m4, alpha 2, and D2 receptors was demonstrated by their ability to inhibit forskolin-stimulated cAMP accumulation with dose-response activities consistent with previous reports for these Gi-coupled receptors. Stimulation of m2, m4, alpha 2, and D2 receptors resulted in an augmentation of ATP-stimulated arachidonic acid release. With the exception of the m4 receptor, none of the receptors tested was able to stimulate arachidonic acid release in the absence of ATP. Potentiation of ATP-stimulated arachidonic acid release was independent of changes in cAMP. The augmentation of ATP-stimulated arachidonic acid release and the inhibition of cAMP accumulation were both blocked by pertussis toxin, an inhibitor of Gi, but with different dose-response characteristics. Inhibition of protein kinase C with staurosporine or long-term pretreatment of the cells with the phorbol ester phorbol 12-myristate 13-acetate blocked the augmentation response. This demonstrates that Gi-coupled inhibitory receptors can amplify ATP-receptor-stimulated arachidonic acid release through a pertussis-toxin-sensitive G protein, independent of their ability to inhibit adenylate cyclase activity.

Discriminatory Effects of Forskolin and EGTA on the Indirect Cyclic AMP Responses to Histamine, Noradrenaline, 5‐Hydroxytryptamine, and Glutamate in Guinea‐Pig Cerebral Cortical Slices

The effects of forskolin (1 microM) and EGTA (5 mM) on indirect cyclic AMP responses in slices of guinea-pig cerebral cortex were examined. Forskolin had little effect on the direct 2-chloroadenosine-stimulated cyclic AMP response. However, it completely abolished the glutamate-induced augmentation of this response. In contrast, forskolin had very little effect on the indirect cyclic AMP responses to noradrenaline, 5-hydroxytryptamine, and histamine. Conversely, rapid removal of extracellular calcium with EGTA 2 min before addition of the indirectly acting agent markedly reduced the augmentation responses produced by these latter agonists, but had little effect on the glutamate augmentation. When EGTA was added once a steady level of cyclic AMP had been achieved with the indirect agents, it was without effect on any of the responses. Thus, calcium appears to have a role in the early, but not the later, stages of the noradrenaline, 5-hydroxytryptamine, and histamine responses. A role for protein kinase C in the glutamate augmentation response was suggested, because forskolin inhibited the augmentation of the 2-chloroadenosine response produced by phorbol esters (which mimic the actions of diacylglycerol in activating protein kinase C). We conclude that there is more than one mechanism by which the augmentation of cyclic AMP responses can occur.

Temporal changes in the calcium‐dependence of the histamine H1‐receptor‐stimulation of cyclic AMP accumulation in guinea‐pig cerebral cortex

1. 2-Chloroadenosine (2CA) causes a maintained rise in adenosine 3':5'-cyclic monophosphate (cyclic AMP) content of guinea-pig cerebral cortical slices which is augmented by addition of histamine. We have investigated the temporal profile of the sensitivity of this response to calcium. 2. Rapid removal of extracellular calcium with EGTA (5 mM) at 2CA (30 microM)-induced steady state caused a slight increase in the cyclic AMP response to 2CA alone and completely abolished the augmentation produced by histamine (0.1 mM) added 20 min later. When EGTA was added only 2 min before histamine, the augmentation was reduced by 72%. 3. The calcium sensitivity of the histamine response was also indicated in studies in which EGTA was added 1 or 3 min after histamine at 2CA-induced steady state. Following addition of EGTA at either of these times, the augmentation was not maintained. 4. When calcium was rapidly removed with EGTA once a steady state level of cyclic AMP had been achieved with histamine, the augmentation response was maintained. This was despite the fact that EGTA had a similar effect on both extracellular free calcium and tissue calcium content when it was applied before or after histamine. 5. The 2CA response was augmented by phorbol esters (which mimic the actions of diacylglycerol) in a calcium-independent manner. 6. These results suggest that calcium is important for the initiation and early stages of the histamine-induced augmentation response. The apparent lack of calcium sensitivity of the response at later stages could mean that calcium is not involved in the maintenance of the response or that the intracellular machinery involved in the augmentation process becomes more sensitive to calcium as the response progresses, such that it becomes able to operate at a much lower level of intracellular calcium. A possible role for diacylglycerol in the maintenance of the response is discussed.

Generation of activated killer (AK) cells by recombinant interleukin 2 (rIL 2) in collaboration with interferon-gamma (IFN-gamma).

Activation of human peripheral blood mononuclear cells (PBMC) by interleukin 2 (IL 2) and the role of interferon-gamma (IFN-gamma) in the IL 2-induced activation were investigated. Activated killer (AK) cells against NK-resistant tumor cell lines were induced in the medium containing recombinant IL 2 (rIL 2) and autologous serum without any other stimulating agents. AK activity was induced by doses of rIL 2 as low as 3 U/ml, and reached a maximum at 10(3) U/ml. Incubation of PBMC with rIL 2 resulted in IFN-gamma production and augmented NK activity after 1 day of culture, and in induction of AK cells and proliferative response after 2 days of culture. These results suggested that endogenous IFN-gamma was required for rIL 2-induction of AK cells and proliferative response. To prove this, PBMC were cultured with rIL 2 and rIFN-gamma or were pretreated with rIFN-gamma before culture with rIL 2. Both rIFN-gamma treatments of PBMC augmented rIL 2-induced AK activity and proliferative response. rIL 2-induced IFN-gamma production was also enhanced by the rIFN-gamma pretreatment of PBMC. The addition of anti-IFN-gamma antibody to rIL 2 cultures abrogated the rIL 2-induced NK augmentation, AK generation, and proliferative response in proportion to the decreased amounts of endogenous IFN-gamma detectable in culture. rIFN-gamma and/or rIL 2 cultures of PBMC increased Tac antigen expression on cell surfaces as measured by flow cytometry. Enhanced Tac expression by rIL 2 was abrogated by adding anti-IFN-gamma antibody. These data indicate that: 1) AK generation and IFN-gamma production are mediated by IL 2, and 2) IFN-gamma production may be required for IL 2 induction of AK cells and proliferative response. These finding are consistent with the hypothesis that AK generation involves a collaboration between IL 2 and IFN-gamma, in which IL 2 stimulates PBMC to produce IFN-gamma, which in turn acts as a differentiation signal that may be involved in the IL 2-initiated AK generation and proliferative response.

Localization of neurotoxic activity of staphylococcal α-hemolysin in the thalamus

Staphylococcal α-hemolysin injected iv into rabbits causes disappearance of brain bioelectric activity. The investigation performed with deep electrodes implanted into thalamic reticular system and motor, somatosensory, and visual regions of the cerebral cortex showed that the most significant disturbances occurred in the thalamic reticular system and somatosensory-visual region of the cerebral cortex. Staphylococcal α-hemolysin evokes an augmentation response as indicated by the EEG tracings. It is postulated that the lethal action of this toxin involves specific structures in the thalamus.

Further investigations on specificity and precision in the Igarashi-McCann FSH assay method.

The Igarashi-McCann method, reported in 1964 as a new biological method assaying FSH with MED corresponded to 2μg equivalents of NIH-FSH-Sl utilizing intact female mice of Swiss-Albino, would be appreciated to be indispensable for sensitive evaluation of FSH, in spite of having been suffered from poor precision which had been destined with the principle of uterine weight augmentation response. The optimum dose of HCG to be added was confirmed to be 0.075 iu through variance analysis of regression line and statistical investigation of linearity and stability in the dose response curve. The limitation and unification of beginning body weight of recipient were concluded to be inevitable not only for improvement of precision but also for qualitative unification in uterine weight response. Utilizing the unified recipient of 8 g, the stable and specific estimation of FSH in normal urine and plasma can be performed within such levels of maximum permitted contaminating dose (MPCD) as 2.0μg equiv. of NTH-LH-S13, 2.5μg equiv. of NIH-GH-S7, 1.0μg equiv. of NIH-GH-HS1082B, 400 mu equiv. of NIH-P-S7, 200mμ equiv. of Armour-ACTH, 200 mu equiv. of NIH-TSH-S5, and 0.005 μg of Estradiol with 0.075 iu of HCG, after referring reported contents of these hormones in pituitary, in plasma, and in urine. In conclusion, the results of Igarashi-McCann assay are specific for FSH, if less than 14.4 μg of rat anterior pituitary extract or less than 2.0ml of rat or human plasma, or 1.0 hr and 0.2 hr equiv. or less of non-pregnant human urinary extract except of acromegaly is injected into one mouse, respectively.

EFFECT OF TESTOSTERONE ON HUMAN CHORIONIC GONADOTROPHIN (HCG)-INDUCED OVARIAN AUGMENTATION IN PARABIOTIC RATS.

The effect of testosterone propionate on castration hypersecretion and the ovarian augmentation reaction to HCG was studied in parabiotic rats. Graded doses of testosterone propionate were administered to castrated (day 30) male or female rats in parabioses with hypophysectomized (day 33) female partners. Steroid administration was initiated on the day of castration and continued for the duration of the experiment. For those hypophysectomized animals receiving HCG, injections were initiated on day 37 and continued for 4 days. Testosterone propionate decreased castration hypersecretion, as evidenced by the reduced ovarian and uterine weights of the hypophysectomized parabiont. The ovarian weights, however, were not reduced to the weight seen in hypophysectomized animals. The ovarian augmentation response to HCG in the hypophysectomized parabiont was essentially the same at all doses of testosterone propionate which inhibited castration hypersecretion. No dose reduced the augmentation reaction to that seen ...