Cyclosporin-A nephrotoxicity and acute cellular rejection in renal transplant recipients: correlation between radionuclide and histologic findings

Serial radionuclide studies using both Tc-99m DTPA (perfusion) and I-131 hippuran (tubular function) were correlated with histologic findings in 25 patients with renal transplants. These cases included 15 cases of cyclosporin-A nephrotoxicity (CsA-NT) and ten cases of acute cellular rejection that were retrospectively selected on the basis of biopsy findings and favorable clinical response to therapy specific for each of these conditions. The serial radionuclide studies enabled the correct diagnosis in 12 of 15 cases of CsA-NT and eight of ten cases of acute rejection. Posttherapy radionuclide studies, furthermore, demonstrated improvement consistent with clinical response. In all cases, the radionuclide results were available at least 24 hours before biopsy findings. These results indicate that serial radionuclide studies evaluating interval changes in both perfusion and tubular function are of significant value in the diagnosis and follow-up of CsA-NT and acute cellular rejection in transplant recipients. This initial experience suggests a sensitivity of 80%.     

Accelerated dissolution of luteal-endometrial integrity by the administration of antagonists of gonadotropin-releasing hormone and progesterone to late-luteal phase women

Sequential blockade of gonadotropin-releasing hormone (GnRH) and progesterone (P) receptors by potent antagonists (Nal-Glu GnRH antagonist and RU486) was conducted in late-luteal phase women to develop a once-a-month birth control method by timed advancement of ongoing luteolysis and endometriolysis. Hormonal dynamics and timing of uterine bleeding during the antagonists' imposed luteal-follicular transition were compared with spontaneous (1st to 2nd) and recovery (2nd to 3rd) cycles in 10 normally cycling women. Serum luteinizing hormone (LH) and follicle-stimulating hormone levels declined (47 +/- 4.3% and 24 +/- 3.0%, respectively) by 24 hours after Nal-Glu injection, which accelerated the ongoing luteolytic process, as evidenced by more rapid declines of serum concentrations of estradiol, P, and ir-inhibin, as compared with the corresponding control cycle. This was accompanied by the prompt (16 +/- 3.2 hours after RU486) onset of a single episode of uterine bleeding, which was advanced by 2 days. Whereas the luteal phase length was foreshortened by 2 days, the subsequent follicular phase duration was prolonged by 2 days with a normal sequence of follicular maturation, LH surge, and luteal function during the recovery cycle. We conclude that the late-luteal sequential administration of antagonists of GnRH and P resulted in acceleration of the ongoing luteolytic and endometriolytic processes without functional alterations of the subsequent cycle.     

Lymphedema of the limb: predictors of efficacy of combined physical therapy

BACKGROUND: Limb lymphedema results from incompetence of the lymphatic system, and treatment of both primary and secondary forms involves manual lymphatic drainage and support. The effectiveness of treatment varies from patient to patient and can be unpredictable.OBJECTIVE: To investigate clinical and paraclinical criteria able to predict responses to combined physical treatment (lymphatic drainage and multilayered support) during hospitalization.PATIENTS AND METHODS: A retrospective study was performed in 45 patients admitted for one week's intensive treatment of limb lymphedema in the Lymphology Unit of the Department of Dermatology of the University Hospital of Tours. Lymphoscintigraphy was performed for all patients on admission. Loss of volume in affected limbs was studied to evaluate the effectiveness of treatment.RESULTS: Two criteria were predictive of resistance to combined treatment, i.e. venous insufficiency and continuing lymph node evidence of scintigraphic activity four hours after lymphoscintigraphy. The two factors were significantly related.CONCLUSION: Failure of combined physical treatment for lymphedema appears to be related to venous insufficiency. It is therefore essential to investigate and treat venous insufficiency, particularly in patients with continuing evidence of scintigraphic activity in lymph nodes.     

Steroids and the reversal of age-associated changes in myelination and remyelination

The myelin sheaths that surround all but the smallest diameter axons within the mammalian central nervous system (CNS) must maintain their structural integrity for many years. Like many tissues, however, this function is prone to the effects of ageing, and various structural anomalies become apparent in the aged CNS. Similarly, the regenerative process by which myelin sheaths, lost as a consequence of exposure to a demyelinating insult, are restored (remyelination) is also affected by age. As animals grow older, the efficiency of remyelination progressively declines. In this article, we review both phenomena and describe how both can be partially reversed by steroid hormones and their derivatives.     

Pregnancy interruption with RU 486 in combination with dl-15-methyl-prostaglandin-F2α-methyl ester: The Chinese experience

In a multicenter study taking place in four centers in Beijing (People's Republic of China), pregnancies up to 49 days of amenorrhea (DA) were interrupted with RU 486 (RU 38486, mifepristone, 600 mg orally once), followed 36–60 hours later by administration of dl-15-methyl-PGF_2α -methyl ester (PG05, 1 mg vaginal suppository). One-hundred-and-sixty women were included in the study, three of whom being excluded from efficacy assessment because of non-compliance to the protocol. Complete pregnancy interruption without additional surgical procedure (success) was obtained in 136 women (86.6%, 95% confidence interval: 81.3–91.9%). The success rate was significantly (P = 0.013) higher for pregnancies below (91.3%), than for pregnancies above 42 days of amenorrhea (DA) (76.6%). The time elapsed between RU 486 intake and complete expulsion was 2.8 ± 1.5 (sd) days (range: 1–12 days). Expulsion took place at the latest 4 days after RU 486 in 125 women (94.7%), and in 107 of these women, it occurred 3.1 ± 1.7 (sd) hours after PG05 administration.Uterine bleeding occurred in all women after RU 486 intake whatever the outcome of treatment and lasted 11.5 ± 4.8 (sd) days (range: 3–36 days). It was judged more or much more abundant than usual periods in 6.15 % of the women. It led to a slight but significant decrease in hemoglobin as measured eight and 14 days after RU 486 intake. In five women, hemoglobin decreased by 4 g/dl or more, but no patient required a blood transfusion. The clinical and biological tolerance of the treatment was otherwise very satisfactory: mild to moderate pain were reported in ~ 80% of the women after PG05, and in ~ 20% of the patients, nausea, vomiting and diarrhea were observed. These were usually moderate, although in one case severe vomiting occurred after RU 486 intake and necessitated vacuum aspiration before PG05 administration. A moderate and transient increase in SGPT (to less than 1.5 times the upper normal limit) was noted in three women after RU 486 and before PG05, and in five women after both RU 486 and PG05.     

Dynamic and static phantoms for evaluation of digital subtraction angiographic systems

Two types of phantoms were developed with which to evaluate the overall performance of digital subtraction angiography (DSA) systems. A dynamic phantom, called a "fish bone" phantom, consists of polyethylene tubes that simulate blood vessels with various lesions, such as stenoses, ulcers, and aneurysms. With this phantom, washout curves were obtained representing the relationship between iodine content and time. It will be useful for qualitative assessment of DSA images, evaluation of different image-processing schemes, and studies of blood flow analysis. A static phantom, called a "C-D" phantom, can be used for measurement of quantitative contrast-detail (C-D) diagrams and for daily monitoring of DSA systems. This was constructed of tubes of seven different diameters (2.15-0.28 mm) and 14 different concentrations of contrast medium (100%-1.1% Renografin-76 [meglumine and sodium diatrizoate]). The C-D diagrams were determined from an observer performance study using C-D phantom images obtained at four different DSA settings.     

Agomelatine (S20098) modulates the expression of cytoskeletal microtubular proteins, synaptic markers and BDNF in the rat hippocampus, amygdala and PFC

Rationale

Agomelatine is described as a novel and clinical effective antidepressant drug with melatonergic (MT₁/MT₂) agonist and 5-HT_2C receptor antagonist properties. Previous studies suggest that modulation of neuronal plasticity and microtubule dynamics may be involved in the treatment of depression.

Objective

The present study investigated the effects of agomelatine on microtubular, synaptic and brain-derived neurotrophic factor (BDNF) proteins in selected rat brain regions.

Methods

Adult male rats received agomelatine (40?mg/kg?i.p.) once a day for 22?days. The pro-cognitive effect of agomelatine was tested in the novel object recognition task and antidepressant activity in the forced swimming test. Microtubule dynamics markers, microtubule-associated protein type 2 (MAP-2), phosphorylated MAP-2, synaptic markers [synaptophysin, postsynaptic density-95 (PSD-95) and spinophilin] and BDNF were measured by Western blot in the hippocampus, amygdala and prefrontal cortex (PFC).

Results

Agomelatine exerted pro-cognitive and antidepressant activity and induced molecular changes in the brain areas examined. Agomelatine enhanced microtubule dynamics in the hippocampus and to a higher magnitude in the amygdala. By contrast, in the PFC, a decrease in microtubule dynamics was observed. Spinophilin (dendritic spines marker) was decreased, and BDNF increased in the hippocampus. Synaptophysin (presynaptic) and spinophilin were increased in the PFC and amygdala, while PSD-95 (postsynaptic marker) was increased in the amygdala, consistent with the phenomena of synaptic remodelling.

Conclusions

Agomelatine modulates cytoskeletal microtubule dynamics and synaptic markers. This may play a role in its pharmacological behavioural effects and may result from the melatonergic agonist and 5-HT_2C antagonist properties of the compound.