Prostaglandin E1-induced Catalepsy in the Rat: Role of Putative Neutrotransmitters

Prostaglandin E₁ (PGE₁) produced dose-related catalepsy in rats when administered intracerebroventricularly. PGE₁ induced catalepsy was significantly inhibited after pretreatment with pharmacological agents known to attenuate central serotonergic and cholinergic activity. It was also inhibited by PGF₂ and naloxone. On the contrary, treatments enhancing central dopaminergic activity also reduced the cataleptic effect of PGE₁. The results suggest that PGE₁ induces catalepsy in rats by modulating activity of central neurotransmitters.     

Subacute (90 days) oral toxicity studies of Kombucha tea

Kombucha tes(KT) is a popular health beverage and is used as an alternative therapy,KT is prepared by placing the kombucha culture in solution of tea and sugar and allowing to ferment,The inoculum is a fungus consisting of symbiotic colony of yeast and bacteria.KT is consumed in several coutries and is believed to have prophylactic and therapeutic benefits in a wide variety of ailments,viz.,intestinal disorders,arthritis,ageing and stiumulation of immunological system.Though KT is used in several parts of the world its eneficial effects and adverse effects have not been scientifically evaluated.Since there are no animal toxicological data on KT,subacute oral toxicity study was carried out.Five goups of rats were maintained:(a) control group given tap water orally,(b) KT given 2ml/kg orally,(c)plain tea(PT) given 2ml/kg orally,(d)KT given in drinking water,1%(v/v)and (e)PT given indrinking water,1%(v/v).The rats were given this treatment daily for a period of 90 days,Weekly records of weight,feed intake,water intake and general behaviour were monitored.There was no significant difference in the growth of the animals as evidenced by the progrssive body weight change.The organ to body weight ration and histologuical evaluation did not show any toxic signs.The haematological and biochemical variables,were within the clinical limits.The study indicates that rats fed KT for 90 day showed no toxic effects.     

Evaluation of beta-tethymustine, a new anticancer compound, in murine tumour models

beta-Tethymustine, 1-[2- {bis(2'-chloroethyl)amino}ethyl]spiro[imidazolidine-4,2'-(1'H),3',4'-dihydronaphthalene]-2,5-dione, has been synthesised and LD50 value determined in Swiss male mice, which was found to be 100.00 mg/kg by single i.p. injection. The following three criteria, namely ascites cell count, ascites fluid measurement and increase in median survival times (MST) of drug-treated (T) over untreated control (C) mice, were studied for evaluation of its antitumour efficacy in vivo in three murine ascites tumours, namely Ehrlich ascites carcinoma (EAC), sarcoma-180 (S-180) and Dalton's lymphoma (DL). At the optimum dose range of 8.0 mg/kg (higher) to 4.0 mg/kg (lower) for 1-7 days treatment following tumour transplantation on day 0, it exhibited a very high percentage of inhibition of both the ascites cell and fluid in these models and displayed excellent ILS(max) value of 80 in EAC, 224 in S-180 and 240 in DL, respectively, showing 'curative' effect (2-3/6 mice having 90 days survival rate). It also demonstrated a high ILS value of 150 with one cure/six mice bearing S-180 for 6 days prior to drug therapy. Screening results were compared with two clinical drugs, cyclophosphamide and 5-fluorouracil, serving as positive controls. Its chemical alkylating activity was compared with nor-HN2 (NSC 10873) and spiromustine (NSC 172112). The results indicate that it possesses greater alkylating activity than nor-HN2 and comparable activity with spiromustine.     

Possible role of dopamine in central effects of cocaine as measured by apomorphine gnawing test in mice

Apomorphine (10 mg/kg, s.c.) does not induce in mice a compulsion to gnaw, but pretreatment with cocaine (10–40 mg/kg, i.p.) caused gnawing activity. This effect of cocaine was inhibited by pretreatment with -methyl-p-tyrosine, haloperidol, and physostigmine, but not with FLA-63, phenoxybenzamine and tetrabenazine. These findings would suggest that dopaminergic mechanism plays a significant role in the potentiation of apomorphine gnawing activity by cocaine and also support the view that inhibition of dopamine uptake is responsible for the stimulatory action of cocaine.     

MRI of the intraorbital optic nerve in patients with autosomal dominant optic atrophy

Measurements of the intraorbital optic nerve were made using high-resolution coronal MRI in 10 adults with autosomal dominant optic atrophy. Comparisons were made with previous studies of 10 normal adult subjects. The cross-sectional diameters of the optic nerve and the perineural subarachnoid space were measured and a ratio of there diameters at anterior, mid and posterior positions along the optic nerve was determined. We found a statistically significant difference in the mean optic nerve: sheath ratio between the control group and patients with autosomal dominant optic atrophy. At anterior, mid and posterior locations along the optic nerve it is significantly smaller in patients with optic atrophy. We have demonstrated that the loss of ganglion cells, previously documented in dominant optic atrophy, is associated with a significant loss of optic nerve tissue and thinning of the nerve along its length. Received: 6 July 1999/Accepted: 22 July 1999     

Evoked potential monitoring in anaesthesia and analgesia

Electrophysiological monitoring of selected neural pathways of the brain, brainstem, spinal cord and peripheral nervous system has become mandatory in some surgery of the nervous system where preventable neural injury can occur. Evoked potentials are relatively simple methods of testing the integrity of various aspects of the nervous system. This review covers the variety of evoked potentials that can be monitored and outlines the principles of their measurement. Their use in specific situations and how factors such as anaesthesia might affect them is presented.     

Impacts of Informal Caregiver Availability on Long-term Care Expenditures in OECD Countries

Objective. To quantify the effects of informal caregiver availability and public funding on formal long-term care (LTC) expenditures in developed countries.
Data Source/Study Setting. Secondary data were acquired for 15 Organization for Economic Cooperation and Development (OECD) countries from 1970 to 2000.
Study Design. Secondary data analysis, applying fixed- and random-effects models to time-series cross-sectional data. Outcome variables are inpatient or home heath LTC expenditures. Key explanatory variables are measures of the availability of informal caregivers, generosity in public funding for formal LTC, and the proportion of the elderly population in the total population.
Data Collection/Extraction Method. Aggregated macro data were obtained from OECD Health Data, United Nations Demographic Yearbooks, and U.S. Census Bureau International Data Base.
Principal Findings. Most of the 15 OECD countries experienced growth in LTC expenditures over the study period. The availability of a spouse caregiver, measured by male-to-female ratio among the elderly, is associated with a $28,840 (1995 U.S. dollars) annual reduction in formal LTC expenditure per additional elderly male. Availability of an adult child caregiver, measured by female labor force participation and full-time/part-time status shift, is associated with a reduction of $310 to $3,830 in LTC expenditures. These impacts on LTC expenditure vary across countries and across time within a country.
Conclusions. The availability of an informal caregiver, particularly a spouse caregiver, is among the most important factors explaining variation in LTC expenditure growth. Long-term care policies should take into account behavioral responses: decreased public funding in LTC may lead working women to leave the labor force to provide more informal care.     

Lack of microvessels in well-differentiated regions of human head and neck squamous cell carcinoma A253 associated with functional magnetic resonance imaging detectable hypoxia, limited drug delivery, and resistance to irinotecan therapy.

PURPOSE: Combination chemotherapy with irinotecan (CPT-11; 50 mg/kg/week x 4 intravenously), followed 24 hour later by 5-fluorouracil (50 mg/kg/week x 4 intravenously), results in 10 and 100% cure rates of animals bearing human head and neck squamous cell carcinoma xenografts A253 and FaDu, respectively. A253 consists of 30% well-differentiated and avascular and 70% poorly differentiated regions with low microvessel density (10/x400), whereas FaDu is uniformly poorly differentiated with higher microvessel density (19/x400). Studies were carried out for determining the role of well-differentiated and avascular regions in drug resistance in A253 and detection of such regions with noninvasive functional magnetic resonance (fMR) imaging. EXPERIMENTAL DESIGN: Tumors were harvested for histopathologic evaluation and immunohistochemistry (CD31, CD34; differentiation marker: involucrin; hypoxia markers: carbonic anhydrase IX, pimonidazole; vascular endothelial factor (VEGF) and Ki67) immediately after fMR imaging following the 3rd dose of chemotherapy. High-performance liquid chromatography determination of intratumoral drug concentration of 7-ethyl-10-hydroxyl-camptothecin and autoradiography with (14)C-labeled CPT-11 was done 2 hours after CPT-11 administration. RESULTS: Although A253 xenografts showed three times higher concentration of 7-ethyl-10-hydroxyl-camptothecin, FaDu was more responsive to therapy. After therapy, A253 tumor consisted mostly (approximately 80%) of well-differentiated regions (positive for involucrin) lacking microvessels with a hypoxic rim (positive for carbonic anhydrase IX and pimonidazole) containing few proliferating (Ki67 positive) poorly differentiated cells. Autoradiography revealed that well-differentiated A253 tumor regions showed 5-fold lower (14)C-labeled CPT-11 concentrations compared with poorly differentiated areas (P < 0.001). Blood oxygen level dependant fMR imaging was able to noninvasively distinguish the hypoxic and well-vascularized regions within the tumors. CONCLUSION: Avascular-differentiated regions in squamous cell carcinoma offer sanctuary to some hypoxic but viable tumor cells (carbonic anhydrase IX and Ki67 positive) that escape therapy because of limited drug delivery. This study provides direct evidence that because of a specific histologic structure, avascular, well-differentiated hypoxic regions in tumors exhibit low drug uptake and represent a unique form of drug resistance.     

High-harmonic spectroscopy of quantum phase transitions in a high-Tc superconductor

We report on the nonlinear optical signatures of quantum phase transitions in the high-temperature superconductor YBCO, observed through high harmonic generation. While the linear optical response of the material is largely unchanged when cooling across the phase transitions, the nonlinear optical response sensitively imprints two critical points, one at the critical temperature of the cuprate with the exponential growth of the surface harmonic yield in the superconducting phase and another critical point, which marks the transition from strange metal to pseudogap phase. To reveal the underlying microscopic quantum dynamics, a strong-field quasi-Hubbard model was developed, which describes the measured optical response dependent on the formation of Cooper pairs. Further, the theory provides insight into the carrier scattering dynamics and allows us to differentiate between the superconducting, pseudogap, and strange metal phases. The direct connection between nonlinear optical response and microscopic dynamics provides a powerful methodology to study quantum phase transitions in correlated materials. Further implications are light wave control over intricate quantum phases, light–matter hybrids, and application for optical quantum computing.

Attosecond technology (1), specifically the process of high harmonic generation (HHG) (2–4), provides an all-optical probe of the microscopic dynamics of atoms, molecules, and solids. Shortly after the first observation of high harmonics in atoms, their generation was understood (4–6) as arising from electron recollision after strong field photoionization and excursion in the continuum. Since the harmonic signal strongly depends on the electron recollision angle and time, high-harmonic spectroscopy (HHS) is a sensitive nonlinear probe of microscopic electronic structure with atomic spatial and suboptical cycle temporal resolution. HHS of solids (7, 8), two-dimensional materials (9, 10), or nanostructured media (11, 12) differs from the gas phase since the optical field–driven electronic wave packet is delocalized over many lattice sites, the wave function depends on the lattice momentum, and a hole has to match the electron’s momentum for recombination to occur (13, 14). Recent experimental efforts extended HHS as nonperturbative probe to quantum materials (9, 10, 15, 16) and to topological insulators (17–19). There have also been several theoretical advances, which suggest using strong fields to probe the physics of Mott insulators (20, 21), alongside the possibility of optically modifying strongly correlated matter (22) and tracking optically induced phase transitions (23), with a recent experiment reported in ref. 24.The sensitivity of HHS to the intricate microscopic details of carriers and lattice predestines HHS to investigate strong interactions and quantum correlations which lead to fascinating new states of matter such as superconductivity. The phase transition into a strongly correlated superconductive state is described by the spontaneous symmetry breaking of the U(1) redundancy when cooling below the critical temperature Tc of the material. As we will show, HHS is a sensitive probe of the dynamic evolution of the superconducting phase transition since the formation of composite bosons by pairing two fermionic spin-1/2 particles (Cooper pairs) changes the distribution of charge carriers, and this sensitively registers in the high harmonic amplitudes and spectral distribution. Pictorially, this is described in SI Appendix, Fig. S1, by a three-step model, consisting of 1) interband excitation process, 2) intraband acceleration, and 3) interband recombination. Pairing below T_c splits the bands by opening a superconducting gap Δ, and in the strongly correlated phase, the three processes of harmonic generation occur within the effective band structure for the Cooper pairs. We will also show that HHS can identify additional phase transitions between quantum phases in the strongly correlated material which are not accessible through the linear optical response, and they are difficult to detect with established methods such as superconducting quantum interference device (SQUID) magnetometry or four-probe transport measurements.A conventional superconductor can be described by the Anderson–Higgs mechanism, which explains that an optical nonlinear response is due to a gapless phase mode (Nambu–Goldstein) and a gapped amplitude mode (Higgs) of the ordering parameter. In the simplest case, and depending on the strength and type of excitation, Boltzmann and Ginzburg–Landau theories (25, 26) predict a second-order response, which mixes with the excitation mode (27, 28), thus the generation of the third harmonic (29). Unconventional high-Tc superconductors are of tremendous interest for a wide range of applications ranging from electronic devices and information processing devices to optical quantum computers and quantum simulators. However, due to their rich landscape of quantum phases and the difficulties of experimental methods to probe the microscopic dynamics, our understanding is still very limited.Among the well-established methods, e.g., transport measurements (30) or magnetic torque measurements (31, 32), photoemission measurements such as angle-resolved photoemission spectroscopy (ARPES) (33, 34) provide direct access to a material’s microscopic carrier distribution and dynamics. The interpretation of such ARPES measurement is, however, complicated by the interpretation of the bulk spectral function and the assumption of independent electron emission despite measuring a strongly correlated electronic state of matter. These are central questions to access the nature of the multibody state, which call for further developments and powerful new tools to aid in the interpretation of the physical mechanism.Therefore, the development of all-optical and ultrafast probes of the macroscopic dynamics inside such materials, which is compatible with existing methods, is highly desirable. To this aim, we apply HHS to investigate the transition between the different phases of the unconventional high-Tc superconductor YBa₂Cu₃O7−d (YBCO). We elucidate the connection between the measured optical spectra, the transition between strange metal and pseudogap phases, and the superconducting phase transition with a strong-field Hubbard model. The HHS measurement clearly shows a departure from the normal conducting phase with an increased formation of Cooper pairs upon cooling. The variation in harmonic orders is linked to phenomenological energy and phase relaxation times, which identify the transition to the fluctuation regime (35, 36), i.e., between the strange metal and pseudogap phases, and the sudden transition at Tc into the superconducting phase. Unconventional superconductors, like YBCO, are material systems in which the formation of composite bosons out of paired fermions is mediated not by phonon exchange but by some other kind of energy exchange (37), for instance, due to spin fluctuations. Such systems present many standing fascinating questions. It is thus important to have new powerful experimental techniques like HHS that provide a fresh and alternate view of the problem.