Chemical constituents and their biological activities from Taunggyi (Shan state) medicinal plants.

Medicinal plants are essential aspects of readily available primary healthcare remedies. Phytochemical constituents of medicinal plants cover a broad variety of chemical fields to explore medicines. This review highlights selected empirical data on traditional uses, phytochemistry, and pharmacological properties of Taunggyi medicinal plants, Andrographis paniculata, Physalis peruviana, and Cassia fistula. Historically, these plants have been used for many infections and diseases in Taunggyi. More than 361 chemical compounds have been isolated and identified from the selected plants. Some of the chemical constituents have substantial pharmacological properties. It is clear that these herbs have significant potential for useful natural supplements in many contemporary diseases. Thus, the aim of this review compiles an ethnobotanical survey and documentation of medicinal plants in Taunggyi (Myanmar). This review will also inspire Myanmar researcher's to further investigate the potential of these plants in their future work into new compound and new drugs.

Anaphylactic shock after synthetic adrenocorticotropin-(1-18) in a patient with isolated adrenocorticotropin and beta-lipotropin deficiency.

A 58-yr-old woman had frequent hypoglycemic attacks, undetectable levels of plasma cortisol, ACTH, and beta-lipotropin, and deficient responses of these hormones after insulin induced-hypoglycemia and metyrapone. Her GH responses to arginine infusion were normal as were her gonadotropin responses to LRH. Her TSH and PRL responses to TRH were abnormally high. Anaphylactic shock occurred after the injection of either synthetic ACTH-Z-(1-24) (Cortrosin-Z) or ACTH-(1-18) (Acthormone). She had received two prior injections of synthetic ACTH-Z-(1-24) 2 months earlier. Circulating anti-ACTH antibody was found in her plasma by radioimmunological methods, but this antibody did not prevent corticosterone production by ACTH in an in vitro ACTH bioassay system. The pathogenic significance of this antibody in the ACTH deficiency is doubtful, and the etiology of the isolated ACTH and beta-LPH deficiency is not clear.

New type of febrifugine analogues, bearing a quinolizidine moiety, show potent antimalarial activity against Plasmodium malaria parasite.

Febrifugine (1) and isofebrifugine (2), isolated from the roots of Dichroa febrifuga Lour. (Chinese name: Cháng Shan), are active principles against malaria. Adducts of 1 and 2 with acetone, Df-1 (3) and Df-2 (4), respectively, were obtained using silica gel and acetone. They showed high activity against P. falciparum malaria in vitro. Compound 3 was found to be equally effective against P. berghei in vivo as the clinically used drug chloroquine, whereas 4 showed only 1/24 of the activity of 3. Metabolism studies of these compounds revealed that compound 4 is readily metabolized in mouse liver. Accordingly, the dose of 4 must be higher than that of 3 to attain blood levels sufficient for a favorable therapeutic effect.

Exploring the structural basis of neurotoxicity in C(17)-polyacetylenes isolated from water hemlock.

Water hemlock, Cicuta virosa, belonging to the Umbelliferae, is well-known as a toxic plant responsible for lethal poisonings in humans as well as animals, causing tonic and clonic convulsions and respiratory paralysis. Cicutoxin (1), being a major violent toxin of the plant, is a chemical in the class of C(17)-polyacetylenes bearing a long pi-bond conjugation system, a terminal hydroxyl, and an allylic hydroxyl in its structure, and a variety of its analogues have been isolated from the plant. In the present study, various derivatives of these toxins were synthesized through acetylation, methylation, and oxidation of cicutoxin (1) and virol A (3) and B (4). 1-Dehydroxyvirol A (28) was prepared through the coupling of (7S)-dodeca-3,5-dien-1-yn-7-ol and 1-iodopentyne under Sonogashira's conditions. A monoacetylenic compound (29) was also prepared through the coupling of (5S)-1-chlorodeca-1,3-dien-5-ol and 1-iodopentyn-5-ol. The structure-activity relationships involved in the acute toxicity of cicutoxin derivatives in mice were investigated, and the length and geometry of pi-bond conjugation and the O-functional groups were found to be important for activity. The potency in inhibition of the specific binding of the noncompetitive GABA antagonist, [(3)H]EBOB, to GABA-gated Cl(-) channels of GABA receptors in rat brain cortex was found to be correlated with acute toxicity, indicating that the ability to bind to these channels plays an important role in the acute toxicity of these compounds.

Virol A, a toxic trans-polyacetylenic alcohol of Cicuta virosa, selectively inhibits the GABA-induced Cl(-) current in acutely dissociated rat hippocampal CA1 neurons.

The effects of virol A (VA), a toxic component of Cicuta virosa (water hemlock), on the GABA-induced Cl(-) current (I(GABA)) in acutely dissociated rat hippocampal CA1 neurons were investigated using whole-cell patch-clamp techniques. VA reversibly reduced I(GABA) and the muscimol (Mus)-induced current (I(Mus)) in a concentration-dependent manner. The IC(50) values for VA against I(GABA) and I(Mus) were 9.6x10(-7) and 9.8x10(-7) M, respectively. VA shifted the EC(50) value of I(GABA) from 6.5x10(-6) to 2.1x10(-5) M, whereas it had no effect on the maximum response, thereby suggesting that VA inhibited I(GABA) in a competitive manner. VA had no apparent effect on current-voltage relationships for I(GABA), thus indicating the lack of voltage-dependency. On the other hand, application of VA (10(-6) M) did not additionally reduce the I(GABA) suppressed by >10(-5) M picrotoxin. VA but not bicuculline accelerated the decay phase of I(GABA), as was seen with picrotoxin. Moreover, pre-application of 10(-5) M VA reduced I(GABA). VA did not inhibit that induced by glycine (10(-4) M). These results indicate that VA inhibits I(GABA) by acting both on the GABA agonist site and on the Cl(-) channel of the GABA(A) receptor-channel complex. VA is a structurally novel type of compound that selectively inhibits the GABA(A) receptor-Cl(-) channel complexes in mammalian central nervous system neurons.

Stimulation of neurotrophic factor secretion from 1321N1 human astrocytoma cells by novel diterpenoids, scabronines A and G.

Glial cells release neurotrophic factors that maintain neurons functionally. When rat pheochromocytoma cells (PC-12) were cultivated with the conditioned medium of human astrocytoma cells (1321N1) incubated with the new diterpenoids, scabronines A and G, isolated from Sarcodon scabrosus, they changed their morphology and there was neurite outgrowth. The scabronines increased the expression of mRNA for nerve growth factor (NGF), and the secretion of NGF from 1321N1 cells in a concentration-dependent manner. However, the enhanced neurite outgrowth produced by the conditioned media was slightly inhibited by NGF neutralizing antibody, and the concentration of NGF released in response to the scabronines was insufficient to cause differentiation. These results suggest that scabronines cause the secretion of other factors together with NGF from 1321N1 cells. The diterpenoids are useful drugs to clarify the mechanism of synthesis and secretion of neurotrophic factors.

Serial MRI and SPECT in amyotrophic lateral sclerosis: a case report.

We report the case of a 42 year-old woman with amyotrophic lateral sclerosis (ALS). Neurological examination showed spastic paraparesis and muscular atrophy of the upper extremities. Increased signal intensity areas were present in the lateral corticospinal tract of the brain and cervical spinal cord on a T2-weighted image. Decreased signal intensity of the motor cortex on the T2-weighted image appeared during the course of the illness. SPECT showed hypoperfusion confined to the motor cortex. The area of increased signal intensity in the cervical spinal cord on the T2-weighted MR images extended to the anterolateral columns of the spinal cord. The area of hypoperfusion in SPECT extended to the fronto-parietal area with the progression of the disease. These changes in the MRI and SPECT findings may reflect progressive degeneration of the upper motor neurons in ALS.

Serial MR findings of chronic idiopathic ataxic neuropathy.

We report the case of a 70-year-old woman with chronic idiopathic ataxic neuropathy. Neurological examination, electrophysiological studies and a sural nerve biopsy suggested involvement of the axon and the dorsal root ganglia. Laboratory examination showed polyclonal elevation of serum IgA. MRI showed high signal intensity in the posterior column of the lumbar spinal cord on T2-weighted images. High signal intensity in the posterior column of the cervical spinal cord on T2-weighted images appeared during the course of the illness. MR abnormalities in this case may reflect the degeneration of the posterior column of the spinal cord subsequent to sensory ganglionic neuropathy.

Isoflavonoid glycosides from Dalbergia sissoo.

Two isoflavone glycosides, biochanin A 7-O-[beta-D-apiofuranosyl-(1-->5)-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside] and tectorigenin 7-O-[beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside], were isolated from Dalbergia sissoo. Their structures were elucidated on the basis of spectral and chemical evidence.

In vivo subcellular elemental dynamics in liver graft: With special reference to effect of non-selective endothelin receptor antagonist, TAK-044, on the graft injury.

Background: No data are available concerning the in vivo subcellular dynamics of elements in liver grafts and the effect of endothelin receptor antagonist, TAK-044, against graft injury. Methods: Liver transplantation was performed in porcine under active veno-venous bypass. The grafts stored in chilled preservation solution were recirculated following reflush with lactated Ringer's solution with or without TAK-044 (10 mg/kg). Cold and warm ischemic times of the grafts were comparable between the two groups. Elements (Na, K, Cl, Ca, P and S) were measured in three fractions of cytoplasm, mitochondria and nucleus by electron probe X-ray microanalysis for the graft biopsy specimens obtained at various time from donor laparotomy to 1 week after liver grafting. Liver functions also were compared between the two groups. Results: In both groups, concentration of each element changed in parallel among the three subcellular fractions and their changes were less marked in the nucleus. In the control group, there were significant increases in cytoplasmic Na and Cl after portal reperfusion and in cytoplasmic and mitochondrial Ca after hepatic artery reperfusion. These were accompanied by K and mitochondrial S decreases without a statistical significance. In the TAK group, such postreperfusion elemental alterations were significantly suppressed and early deterioration of the liver functions was alleviated, as compared with the control group. Conclusion: A supplemental use of TAK-044 in a rinse solution before reflush contributed to stability of subcellular elements after reperfusion and better preservation of early graft function.

Changes in the molecular sieve of glomerular basement membrane in rats with aminonucleoside nephrosis.

Isolated and purified glomerular basement membranes (GBM) of normal and aminonucleoside (PAN) nephrosis rats were observed by electron microscopy after negative staining. Although GBM of normal rats appeared as a molecular sieve with uniform pores, GBM of nephrotic rats showed enlargement and elongation of the pores. For an average of fifty pores, the long dimension was 40.4+/-10.7 A and the short dimension 13.8+/-3.6 A in nephrosis whereas the long dimension was 12.3+/-2.5 A and the short dimension 8.4+/-1.0 A in normal rats. Changes in the pores in GBM were thought to result in increased permeability of serum protein and hence proteinuria.

Detection of DR antigen on leukemic cells from a patient suffering from adult T-cell leukemia and progressive systemic sclerosis.

This report concerns an unusual case of adult T cell leukemia (ATL) complicated with progressive systemic sclerosis (PSS). The surface markers of peripheral blood mononuclear cells (PBM) and lymph node cells, both of which mainly consisted of leukemic cells, were examined. The effect of these cells on the pokeweed mitogen (PWM)-induced IgG synthesis by normal PBM also was studied. The leukemic cells formed rosettes with sheep red blood cells (SRBC; E) and expressed T cell antigen, Leu-1, and DR antigen. The detection of cell surface antigens was carried out by employing monoclonal antibodies against these antigens. We diagnosed this case as DR positive ATL. In terms of the immunoregulatory function of these leukemic cells, the co-culture experiments showed that these cells had some suppressive effect on the PWM-induced IgG production by allogeneic normal PBM.

Ultrastructure of rat renal tubular basement membrane--meshwork structure demonstration by negative staining.

The tubular basement membrane (TBM) (i.e. tubular basal lamina) of rat kidney was shown to be a fine meshwork by electron microscopy after negative staining. Strands of the meshwork formed a regular three dimensional lattice work. The pores of the meshwork were polygonal. There were two main pore sizes: one approximately 30 A in diameter, the other 42--60 A. In view of our previous observation that glomerular and alveolar basement membranes were made up fine meshwork, it is quite possible that the basement membranes of other organs are also made up such fine meshwork.

Anti-tumor activity of squid ink.

The anti-tumor activity of a new type of peptidoglycan isolated from squid ink was shown to have a cure rate of 64% for Meth A tumor from BALB/c mice. The ink delipidated in acetone, which contained the peptidoglycan at 0.1% (w/w), was administered to tumor-transplanted mice so as to examine the anti-tumor activity. One-fifth of the tumor-bearing mice was cured with 3 injections (1 mg/head) of the acetone delipidated squid ink or a prolongation of survival was observed in the treated animals. Heat treatment at 100 degrees C for 10 min did not affect the anti-tumor activity of the delipidated ink, its potentiality being preserved. The acetone-extractable fraction of the ink also brought about a similar cure rate for Meth A tumor. The delipidated ink enhanced the phagocytic activity of macrophages but no direct cytotoxicity was observed for the Meth A tumor cells. Hence it may be said that the anti-tumor activity of the delipidated ink was mainly due to the augmented cellular immunity in vivo.

[Biological activities of natural resources around us are now in the limelight].

There are various kind of natural resources around us, and they must contain a lot of unknown bioactive substances. Some may be structurally very strange for us, and some are very familiar. But their biological activity was not unfortunately investigated in detail. Accordingly, exploring new types of pharmaceutical resources may give lead compounds of the drugs in the future. Among those natural resources, I examined squid ink and scallop soup. From squid ink, an antitumor glycoconjugate was obtained. Its polysaccharide moieties, illexin A, illexin B and illexin C, were isolated, and the spectral data and chemical transformation of their acid hydrolysate revealed to bear a unique branched repeating unit, [-3GlcA beta 1-4(GalNAc alpha 1-3)Fuc alpha 1-]n. Moreover, scallop soup gave antitumor glycogen by the action of protease. The fine structure of glycogen was investigated by the sequential enzyme digestion method using beta-amylase and pullulanase, while the unit chain was analyzed by high performance anion exchange chromatography. The results showed that the antitumor active glycogen was highly branched with shorter chain than glycogens without antitumor activity.

[A case of Marchiafava-Bignami disease that responded to high-dose intravenous corticosteroid administration].

We report a 63-year-old male who presented acute confusional state with prominent rigidity of all extremities. The patient had a long history of alcoholism and was in poor physical condition and malnourished. The diagnosis of Marchiafava-Bignami disease was indicated by T2-weighted MRI demonstrating high signal intensity in the corpus callosum. Because Wernicke's encephalopathy was suspected as a complication, thiamine therapy was applied, but there was no clinical improvement. Immediately after high-dose intravenous corticosteroid administration was started, his symptoms rapidly resolved except for mild cognitive impairment. It is supposed that edematous change in the early stages of Marchiafava-Bignami disease causes impairment of the blood-brain barrier. Steroid therapy may prevent such a process by means of its the anti-edema effect and by normalizing blood-brain barrier. The present case suggests that corticosteroid therapy has beneficial effects for Marchiafava-Bignami disease.

[HTLV-I associated myelopathy (HAM) with cerebellar atrophy presenting a down-beat nystagmus].

A 67-year-old woman began to have difficulty in walking due to spastic paraparesis, sensory impairment in the lower limbs and instability on standing at the age of 59 years. Eight years later, she developed complete spastic paraplegia and urinary incontinence. On examination, she was found to have down-beat nystagmus and ocular hypermetria. Brain CT scan and MRI revealed cerebellar atrophy, predominantly in the vermis. HTLV-I antibody titer was increased in both serum and cerebrospinal fluid (CSF). She was diagnosed as having HAM and placed on prednisolone, salazosulfapyridine and high-dose vitamin C. Her symptoms including gait disturbance, nystagmus and ocular hypermetria improved but did not completely disappear. In parallel with clinical improvement, the antibody titer to HTLV and the ratio of CD4/CD8 lymphocyte subsets in blood decreased. The above observations suggest that the cerebellar signs and cerebellar atrophy share the same etiology with HAM. The presence of nystagmus and prominent cerebellar signs plus the CT and MRI findings strongly suggest that the lesions in HAM are not limited to the spinal cord but extend to the brainstem and cerebellum.

[A case of toxoplasmic chorioretinitis and meningoencephalitis in an immunocompetent adult].

A 71-year-old man who presented with toxoplasmic chorioretinitis and meningoencephalitis is reported. He had been healthy and immunologically normal. Initially, he complained of blurring of vision without headache, nor fever. Neurological examinations revealed papilledema, nuchal rigidity, and disorientation. Fluorescent angiography of the ocular fundi disclosed hyperfluorescent leaks suggesting chrioretinitis. His EEG had dysrhythmic slow alpha wave with some theta slowing. CSF studies showed pleocytosis up to 80/mm3; the cells were predominantly lymphocytes. The titers of toxoplasma antibody in the serum and CSF were prominently increased. Toxoplasmosis was highly suspected and he was treated with predinsolone, acetylspiramycin, and pyrimethamine. After the treatment, ophthalmologic and neurological symptoms improved, and the laboratory findings including the titers of toxoplasma antibody in the serum and CSF were also improved. Recently, toxoplasmosis associated with neurological complications as an opportunistic infection is a serious problem in the immunocompromised hosts, especially in AIDS, but this infection is rare in immunologically normal adults. Our case and some other reports may suggest a chance of developing toxoplasmic meningoencephalitis even in healthy individuals. We have to think of the possibility of toxoplasmosis in the immunocompetent hosts when they are presenting with chorioretinitis and meningoencephalitis.

[Dissociated adduction nystagmus in a patient with hereditary spinocerebellar degeneration].

A 66-year-old woman with a 10 years' history of autosomal dominant hereditary spinocerebellar degeneration developed an atypical nystagmus. Neurological examination revealed cerebellar ataxia, absent tendon reflex, supranuclear upward gaze palsy, saccadic pursuit and nystagmus. Nystagmus was a dissociated type and appeared only in lateral gaze and the amplitude was prominent in adducting eyes. Brain MRI showed cerebellar hemispheric and vermal atrophy, and pontine atrophy. Neuro-otological examination revealed normal caloric test, but impaired optokinetic nystagmus and visual suppression test. The dissociated adduction nystagmus of this case may correspond to gaze evoked nystagmus and latent hypofunction of the abducens motor neurons.

[Efficacy of TRH-T for spinocerebellar degeneration--the relation between clinical features and effect of TRH therapy].

Thyrotropin releasing hormone (TRH) therapy has been frequently attempted for the treatment of spinocerebellar degeneration (SCD) and its efficacy has been confirmed. However, effectiveness is considered to differ depending on disease type, severity and the method of evaluating clinical improvement. We investigated the efficacy of thyrotropin releasing hormone-tartrate (TRH-T) in 23 patients with SCD consisting of cerebellar form (cortical cerebellar atrophy (CCA) and hereditary cortical cerebellar atrophy (H-CCA)), and multiple system form (multiple system atrophy (MSA) and hereditary olivopontocerebellar atrophy (H-OPCA)). TRH-T, 2 mg per day, was given intravenously for 20 days. The effect of TRH therapy was evaluated by assessing changes in balance function while lying, sitting, standing and walking, that may reflect the movement functions in active daily life (ADL) for the patients with SCD. The speech function was also evaluated qualitatively using acoustic analysis. The amine metabolites (HVA and 5-HIAA) in cerebrospinal fluid possibly reflecting the noradrenaline and serotonin metabolism in the central nervous system were measured before and after treatment. Although mild or moderate improvement of the balance function during the course of TRH therapy was seen in 16 of the 23 patients, patients with cerebellar forms (CCA and H-CCA) improved significantly as compared to patients with MSA. The effect persisted for a long time (mean; 3.8 months) after TRH therapy in nine of the 16 patients, and eight (88.9%) of the nine had the cerebellar form of SCD. The levels of HVA and 5-HIAA in CSF also increased in patients with CCA as compared to patients with MSA and H-OPCA. The disease severity before the treatment in 14 (87.5%) of 16 patients who showed improvement of balance functions by TRH therapy was mild or moderate; possible of walking without support, or occasionally with support. Considering these results together, TRH therapy may be effective in patients with the cerebellar form of SCD, whose illness severity is mild, and may be recommended for support of ADL in patients with the cerebellar form of SCD.