Pharmacology and Ethnomedicinal Potential of Selected Plants Species from Apiaceae (Umbelliferae).

BACKGROUND: The Apiaceae or Umbelliferae is one of the largest families in terms of species representation in the plant kingdom. It is also a prominent family in the field of phytochemicals and pharmacology. The family is also quite prominent in the production of spices and condiments and food supplements in nutrition, aside from the potential of species in the family to induce apoptotic, antimicrobial, antitumor, and hepatoprotective activities. OBJECTIVE: This work presents a detailed structural elucidation and functional aspects of phytochemicals from the Apiaceae or Umbelliferae family. METHODS: Furthermore, the application of members of this family in traditional and modern pharmacology is emphasized. This review also highlights the linkage of phytochemicals used in the conventional system of medication for the development of novel therapeutics through a chain of pre-clinical and clinical trials. CONCLUSION: This study may represent a valuable step ahead in the clinical development of natural drugs for curing several ailments, including respiratory and virus-related diseases.

Variability in empathic fear response among 11 inbred strains of mice.

Empathy is an important emotional process that involves the ability to recognize and share emotions with others. We have previously developed an observational fear learning (OFL) behavioral assay to measure empathic fear in mice. In the OFL task, a mouse is conditioned for context-dependent fear when it observes a conspecific demonstrator receiving aversive stimuli. In the present study, by comparing 11 different inbred mouse strains that are commonly used in the laboratory, we found that empathic fear response was highly variable between different strains. Five strains--C57BL/6J, C57BL/6NTac, 129S1/SvImJ, 129S4/SvJae and BTBR T(+) Itpr3(tf) /J--showed observational fear (OF) responses, whereas AKR/J, BALB/cByJ, C3H/HeJ, DBA/2J, FVB/NJ and NOD/ShiLtJ mice exhibited low empathic fear response. Importantly, day 2 OF memory was significantly correlated with contextual memory in the classical fear conditioning among the 11 strains. Innate differences in anxiety, locomotor activity, sociability and preference for social novelty were not significantly correlated with OFL. Interestingly, early adolescent C57BL/6J mice exhibited an increase in acquisition of OF. The level of OFL in C57BL/6J strain was not affected by sex or strains of the demonstrator. Taken together, these data strongly suggest that there are naturally occurring OFL-specific genetic variations modulating empathic fear behaviors in mice. The identification of causal genes may uncover novel genetic pathways and underlying neural mechanisms that modulate empathic fear and, ultimately, provide new targets for therapeutic intervention in human mental disorders associated with impaired empathy.

Xylitol production from a mutant strain of Candida tropicalis.

AIMS: To characterize the kinetics of growth, sugar uptake and xylitol production in batch and fed-batch cultures for a xylitol assimilation-deficient strain of Candida tropicalis isolated via chemical mutagenesis. METHODS AND RESULTS: Chemical mutagenesis using nitrosoguanidine led to the isolation of the xylitol-assimilation deficient strain C. tropicalis SS2. Shake-flask fermentations with this mutant showed a sixfold higher xylitol yield than the parent strain in medium containing 25 g l⁻¹ glucose and 25 g l⁻¹ xylose. With 20 g l⁻¹ glycerol, replacing glucose for cell growth, and various concentrations of xylose, the studies indicated that the mutant strain resulted in xylitol yields from xylose close to theoretical. Under fully aerobic conditions, fed-batch fermentation with repeated addition of glycerol and xylose resulted in 3.3 g l⁻¹ h⁻¹ xylitol volumetric productivity with the final concentration of 220 g l⁻¹ and overall yield of 0.93 g g⁻¹ xylitol. CONCLUSIONS: The xylitol assimilation-deficient mutant isolated in this study showed the potential for high xylitol yield and volumetric productivity under aerobic conditions. In the evaluation of glycerol as an alternative low-cost nonfermentable carbon source, high biomass and xylitol yields under aerobic conditions were achieved; however, the increase in initial xylose concentrations resulted in a reduction in biomass yield based on glycerol consumption. This may be a consequence of the role of an active transport system in the yeast requiring increasing energy for xylose uptake and possible xylitol secretion, with little or no energy available from xylose metabolism. SIGNIFICANCE AND IMPACT OF THE STUDY: The study confirms the advantage of using a xylitol assimilation-deficient yeast under aerobic conditions for xylitol production with glycerol as a primary carbon source. It illustrates the potential of using the xylose stream in a biomass-based bio-refinery for the production of xylitol with further cost reductions resulting from using glycerol for yeast growth and energy production.

Minimal alterations in T-type calcium channel gating markedly modify physiological firing dynamics.

T-type calcium channel isoforms expressed in heterologous systems demonstrate marked differences in the biophysical properties of the resulting calcium currents. Such heterogeneity in gating behaviour not only reflects structural differences but is also observed following the regulation of channel activity by a number of ligands. However, the physiological impact of these differences in gating parameters of the T channels has never been evaluated in situ where the unique interplay between T-type calcium and other intrinsic currents is conserved, and T channel activation can be triggered by synaptic stimulation. Here, using the dynamic clamp technique, artificial T conductances were re-incorporated in thalamic neurons devoid of endogenous T currents to dissect the physiological role of the T current gating diversity on neuronal excitability. We demonstrate that the specific kinetics of the T currents in thalamocortical and nucleus reticularis thalami neurons determine the characteristic firing patterns of these neurons. We show that subtle modifications in T channel gating that are at the limit of the resolution achieved in classical biophysical studies in heterologous expression systems have profound consequences for synaptically evoked firing dynamics in native neurons. Moreover, we demonstrate that the biophysical properties of the T current in the voltage region corresponding to the foot of the activation and inactivation curves drastically condition physiologically evoked burst firing with a high degree of synaptic input specificity.

A comparative study of perchlorate degradation in acute toxicity and chronic toxicity.

Since the discovery of perchlorate in water system, the public has been concerned about its human health effect. In practice it was reported that chronic exposure to perchlorate may lead to damage in thyroid hormone activity. This study introduced a method of perchlorate reduction, using autotrophic bacteria which utilise hydrogen as an electron donor. Two experiments were conducted to compare the effects of acute and chronic perchlorate toxicity on bacterial perchlorate reduction potential. One was a batch-fed operation generating acute toxicity and another was a continuous-fed operation generating chronic toxicity. Acclimation period of the batch-fed operation was 14 days while that of the continuous-fed operation was 31 days as commensurate with double. Lots of batch tests using the mixed culture passing through acclimation were conducted to figure out kinetics of biological perchlorate reduction. The maximum perchlorate utilisation rate (q(max)) of the mixed culture acclimated by acute toxicity was 2.92 mg ClO(4)(-)/mg dry-weight (DW)/d, while that of chronic toxicity was 0.27 mg ClO(4)(-)/mg DW/d. Half-maximum rate constants (K(s)) of acute and chronic toxicity were 567.3 and 25.6 mg ClO(4)(-)/L respectively. This result showed that acute toxicity acclimated the mixed culture more rapidly and produced a higher activity for biological perchlorate reduction than chronic toxicity.

The rgg gene is a specific marker for Streptococcus oralis.

Although the pathogenesis of Streptococcus oralis may be different from that of other viridans group streptococci, S. oralis shares a high degree of DNA sequence similarity with these streptococci. As a result, discrimination of S. oralis from its close relatives has long been considered difficult. This study was conducted to find specific genes that allow for the in vitro identification of S. oralis, but not other oral commensals. Four hundred ninety S. oralis clones obtained by suppressive subtractive hybridization were used for Southern hybridization, and positive clones were sequenced. Of 5 S. oralis-specific clones, newly designed primer sets based on the glucosyltransferase regulatory gene amplified genomic DNA only from S. oralis strains, but not from any of the other 125 strains tested. Our findings may be useful for the future development of efficient diagnostic tools for the rapid identification and differentiation of S. oralis from other oral streptococci strains.

Effect of bone block graft with rhBMP-2 on vertical bone augmentation.

The effectiveness of vertical bone augmentation was evaluated in the cranial bone of 15 rabbits using a block of deproteinized bovine bone plus 10% porcine collagen (DBBB) and a cortico-cancellous human bone block (CHBB) with recombinant human bone morphogenetic protein-2 (rhBMP-2) in comparison with a guided bone regeneration (GBR) technique. The rabbits were divided into six groups: DBBB alone, DBBB/rhBMP-2, DBBB/membrane, CHBB alone, CHBB/rhBMP-2 and CHBB/membrane groups. After 12 weeks, the rabbits were killed. The CHBB groups showed higher values than the DBBB groups in terms of vertical height, the area of new bone fill and the maintained grafted area. In the CHBB groups, the CHBB/rhBMP-2 group revealed similar results to GBR. This animal study verifies that a CHBB with rhBMP-2 could be an alternative treatment option for vertical bone augmentation.

Deficits in social behavior and sensorimotor gating in mice lacking phospholipase Cbeta1.

Abnormal phospholipid metabolism has been implicated in the pathogenesis of schizophrenia, and it was reported that phospholipase C (PLC) beta1 is reduced in specific brain areas of patients with schizophrenia. However, the causal relationship of the PLCbeta1 gene with behavioral symptoms of schizophrenia remains unclear. To address this issue, we have examined the mutant mice lacking PLCbeta1 for schizophrenia-related phenotypes by performing various behavioral tests, including general locomotor activity, sensorimotor gating, social behaviors, and learning and memory. Phospholipase C beta1 knockout mice showed hyperactivities in an open field. They showed impaired prepulse inhibition of acoustic startle response, which was ameliorated by a systemic administration of an antipsychotic D2-receptor antagonist, haloperidol. In addition, they showed abnormal social behaviors, such as lack of barbering behavior, socially recessive trait and lack of nesting behavior. Furthermore, they showed impaired performance in the delayed-non-match-to-sample T-maze test. The present results show that the PLCbeta1 mutant mice share some of the behavioral abnormalities that have been reported in patients with schizophrenia. Thus, the PLCbeta1-linked signaling pathways may be involved in the neural system whose function is disrupted in the pathogenesis of schizophrenia.

Phospholipase C-beta1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration.

Phospholipase C-beta1 (PLC-beta1) is a rate-limiting enzyme implicated in postnatal-cortical development and neuronal plasticity. PLC-beta1 transduces intracellular signals from specific muscarinic, glutamate and serotonin receptors, all of which have been implicated in the pathogenesis of schizophrenia. Here, we present data to show that PLC-beta1 knockout mice display locomotor hyperactivity, sensorimotor gating deficits as well as cognitive impairment. These changes in behavior are regarded as endophenotypes homologous to schizophrenia-like symptoms in rodents. Importantly, the locomotor hyperactivity and sensorimotor gating deficits in PLC-beta1 knockout mice are subject to beneficial modulation by environmental enrichment. Furthermore, clozapine but not haloperidol (atypical and typical antipsychotics, respectively) rescues the sensorimotor gating deficit in these animals, suggesting selective predictive validity. We also demonstrate a relationship between the beneficial effects of environmental enrichment and levels of M1/M4 muscarinic acetylcholine receptor binding in the neocortex and hippocampus. Thus we have demonstrated a novel mouse model, displaying disruption of multiple postsynaptic signals implicated in the pathogenesis of schizophrenia, a relevant behavioral phenotype and associated gene-environment interactions.

Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels.

Although T-type Ca(2+) channels are implicated in nociception, the function of specific subtypes has not been well defined. Here, we compared pain susceptibility in mice lacking Ca(V)3.2 subtype of T-type Ca(2+) channels (Ca(V)3.2(-/-)) with wild-type littermates in various behavioral models of pain to explore the roles of Ca(V)3.2 in the processing of noxious stimuli in vivo. In acute mechanical, thermal and chemical pain tests, Ca(V)3.2(-/-) mice showed decreased pain responses compared to wild-type mice. Ca(V)3.2(-/-) mice also displayed attenuated pain responses to tonic noxious stimuli such as intraperitoneal injections of irritant agents and intradermal injections of formalin. In spinal nerve ligation-induced neuropathic pain, however, behavioral responses of Ca(V)3.2(-/-) mice were not different from those of wild-type mice. The present study reveals that the Ca(V)3.2 subtype of T-type Ca(2+) channels are important in the peripheral processing of noxious signals, regardless of modality, duration or affected tissue type.

Impaired long-term memory and long-term potentiation in N-type Ca2+ channel-deficient mice.

Voltage-dependent N-type Ca(2+) channels, along with the P/Q-type, have a crucial role in controlling the release of neurotransmitters or neuromodulators at presynaptic terminals. However, their role in hippocampus-dependent learning and memory has never been examined. Here, we investigated hippocampus-dependent learning and memory and synaptic plasticity at hippocampal CA3-CA1 synapses in mice deficient for the alpha(1B) subunit of N-type Ca(2+) channels. The mutant mice exhibited impaired learning and memory in the Morris water maze and the social transmission of food preference tasks. In particular, long-term memory was impaired in the mutant mice. Interestingly, among activity-dependent long-lasting synaptic changes, theta burst- or 200-Hz-stimulation-induced long-term potentiation (LTP) was decreased in the mutant, compared with the wild-type mice. This type of LTP is known to require brain-derived neurotrophic factor (BDNF). It was found that both BDNF-induced potentiation of field excitatory postsynaptic potentials and facilitation of the frequency of miniature excitatory postsynaptic currents (mEPSCs) were reduced in the mutant. Taken together, these results demonstrate that N-type Ca(2+) channels are required for hippocampus-dependent learning and memory, and certain forms of LTP.

Variations in the behaviors to novel objects among five inbred strains of mice.

Novelty stimuli cause various behavioral responses, such as exploration and avoidance, and contextual variables may contribute to the behavioral outputs. Here, we tried to compare the behavioral responses to novel objects of five inbred strains of mice (C57BL/6J, 129/svJae, C3H/HeJ, BALB/cJ and DBA/2J) by using a modified novel object test where a small light-weight cube wrapped with paper was presented to mice in a home cage without beddings. In response to these objects, the C57BL/6J, 129/svJae and C3H/HeJ mice showed mild exploratory behaviors, such as approaching, sniffing or brief contact. In striking contrast, the BALB/cJ and DBA/2J mice, which have been known to show high avoidance/low exploration in other behavioral paradigms, exhibited play-like secondary reactions toward the objects after initial primary exploratory behaviors. Specifically, DBA/2J mice would move the object around in the cage, holding it with their mouths, and BALB/cJ mice would gnaw the object, eventually stripping off the wrapping paper. Such behaviors decreased when similar objects were presented repeatedly. The present results suggest that active manipulations of novel objects may be a relevant parameter for measuring novelty-induced behaviors in mice and appear to be strongly influenced by genetic factors.

Performance comparison of a continuous-flow stirred-tank reactor and an anaerobic sequencing batch reactor for fermentative hydrogen production depending on substrate concentration.

This study was conducted to compare the performance of a continuous-flow stirred-tank reactor (CSTR) and an anaerobic sequencing batch reactor (ASBR) for fermentative hydrogen production at various substrate concentrations. Heat-treated anaerobic sludge was utilized as an inoculum, and hydraulic retention time (HRT) for each reactor was maintained at 12 h. At the influent sucrose concentration of 5 g COD/L, start-up was not successful in both reactors. The CSTR, which was started-up at 10 g COD/L, showed stable hydrogen production at the influent sucrose concentrations of 10-60 g COD/L during 203 days. Hydrogen production was dependent on substrate concentration, resulting in the highest performance at 30 g COD/L. At the lower substrate concentration, the hydrogen yield (based on hexose consumed) decreased with biomass reduction and changes in fermentation products. At the higher substrate concentration, substrate inhibition on biomass growth caused the decrease of carbohydrate degradation and hydrogen yield (based on hexose added). The ASBR showed higher biomass concentration and carbohydrate degradation efficiency than the CSTR, but hydrogen production in the ASBR was less effective than that in the CSTR at all the substrate concentrations.

Biological nutrient removal in simple dual sludge system with an UMBR (upflow multi-layer bioreactor) and aerobic biofilm reactor.

In this study, a simple dual sludge process was developed for small sewage treatment. It is a hybrid system that consists of upflow multi-layer bioreactor (UMBR) as anaerobic and anoxic reactor with suspended growth microorganisms and post aerobic biofilm reactor with inclined plates. UMBR is a multifunction reactor that acts as primary sedimentation tank, anaerobic reactor, anoxic reactor, and thickener. The sludge blanket in the UMBR is maintained at a constant level by automatic control so that clear water (30 mg-SS/L) can flow into the post aerobic biofilm reactor. It leads to improving performance of the biofilm reactor due to preventing of excess microbial attachment on the media surface and no requirment for a large clarifier caused by low solid loading. The HRT in the UMBR and the aerobic biofilm reactor were about 5.8 h and 6.4 h, respectively. The temperature in the reactor during this study varied from 12.5 degrees C to 28.3 degrees C. The results obtained from this study show that effluent concentrations of TCOD, TBOD, SS, TN, and TP were 29.7 mg/L, 6.0 mg/L, 10.3 mg/L, 12.0 mg/L, and 1.8 mg/L, which corresponded to a removal efficiency of 92.7%, 96.4%, 96.4%, 74.9%, and 76.5%, respectively. The sludge biomass index (SBI) of the excess sludge in the UMBR was about 0.55, which means that the sludge in the UMBR was sufficiently stabilized and may not require further treatment prior to disposal.