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BACKGROUND: Amoora rohituka is described in Ayurveda, an Indian traditional system of medicine for management of disorders of blood, diseases of eye, helminthiasis disease, ulcer, liver disorders and splenomegaly. However, the leaves were not reported to have anticancer properties till date. OBJECTIVE: This study was carried out to evaluate the cytotoxic potential of leaf extracts of Amoora rohituka. MATERIALS AND METHODS: The leaves powder was macerated in petroleum ether, ethyl acetate and methanol and evaluated their anticancer activities in vitro. The phytochemical constituents of the active (ethyl acetate) extract were screened by FTIR analysis and phytochemical screening methods. RESULTS: The ethyl acetate extract (RLEA) showed the presence of alkaloids, flavonoids, steroids, tannins, saponins and terpenoids. The RLEA exhibited high cytotoxic effect against human breast cancer cells, MCF-7 (IC50 = 9.81 µg/mL) and induced apoptosis by altering nuclear morphology and DNA laddering. Wound healing assays explained the potency of extract to decrease the cell migration. CONCLUSION: The extract of Amoora rohituka leaves exhibited anticancer activity with less toxicity and it could be used for development of alternative drugs in the treatment of human breast cancer.

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Pyknodysostosis is an extremely rare lysosomal storage disease of the bone. Osteosclerosis of the skeleton is due to a decrease of the bone turnover. A plethora of clinical and radiological findings are observed. Patients are short statured with acroosteolysis and dense bones and develop multiple spontaneous bone fractures. A female patient presented with frontal bossing, small and thick fingers and toes. The classical clinical and radiological findings confirmed it as pyknodysostosis.

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We present a rarest of rare case of Tetra-Phocomelia evaluated by antenatal Ultrasonography. It is a condition seen in 0.62 per 100,000 live births. An ultrasonogram was done at 18 wk of pregnancy to assess the fetus and after termination gross specimen was evaluated and X-ray infantograms were done to confirm the findings. The case showed classic Tetra-Phocomelia with limbs like flippers of a seal. Our findings make it rarest of rare as only few cases have been so far reported.

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INTRODUCTION: Penile fracture is an uncommon and less reported condition. Early diagnosis with corrective measures is the order of the day. AIM: To perform ultrasonography of penis and to understand its role in making correct diagnosis of fractures. To know how it will help surgeon in its management and in adopting a grading system. MATERIALS AND METHODS: Emergency evaluation of 15 cases of penile fractures by ultrasonography before surgery. Entire penis was scanned all along its length and circumference. Tunica albugenia was seen as white covering of both corpora cavernosa and break in its continuity is seen as wedge shape defect. Hematoma on either sides of tunica was well appreciated. RESULTS: After ultrasonography all patients underwent emergency surgery, the defect in corpora was well appreciated. Repair of tunica albugenia was done which confirmed our findings. CONCLUSION: Ultrasonography is the modality of choice for quick diagnosis, and no other radiological workup is required before surgery.

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The current work focuses on the study of polymeric, biodegradable nanoparticles (NPs) for the encapsulation of doxorubicin and mitomycin C (anti-leishmanial drugs), and their efficient delivery to macrophages, the parasite's home. The biodegradable polymer methoxypoly-(ethylene glycol)-b-poly (lactic acid) (MPEG-PLA) was used to prepare polymeric NPs encapsulating doxorubicin and mitomycin C. The morphology, mean diameter, and surface area of spherical NPs were determined by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and BET surface area analysis. X-ray diffraction was performed to validate drug encapsulation. An in vitro release profile of the drugs suggested a fairly slow release. These polymeric NPs were efficiently capable of releasing drug inside macrophages at a slower pace than the free drug, which was monitored by epi-fluorescence microscopy. Encapsulation of doxorubicin and mitomycin C into NPs also decreases cellular toxicity in mouse macrophages (J774.1A).

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We report here the effect of iridoid glucosides, isolated from Nyctanthes arbortristis, on redox homeostasis of Leishmania parasite. These compounds led to an increase in reactive oxygen species by inhibiting a crucial enzyme of redox metabolism of the parasite. Our experiments clearly showed that these compounds are highly active as antileishmanial agents. The in vitro experiments on intra-macrophageal amastigotes showed significant killing of parasite even at very low concentration. Determination of mechanism of action of iridoid glucosides showed that increased ROS level leads to oxidative stress, cell membrane damage and apoptosis of Leishmania sp. Our cellular toxicity assays on Human embryonic kidney (HEK 293) and mouse macrophage (J774A.1) cell lines showed these compounds to be very safe for therapeutics application.

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Trypanothione and trypanothione reductase (TryR)-based redox metabolism found in Leishmania and other trypanosomatids exemplify the unique features of this group of organisms. Its absence in mammalian hosts, together with the sensitivity of trypanosomes against oxidative stress, makes this enzyme a unique target for exploitation for potential antileishmanial chemotherapeutics. Plumbagin, a plant-derived naphthoquinone, is reported to possess antileishmanial properties by inhibiting TryR. We here report the kinetics of the inhibitory mechanism of plumbagin and its derivative, 2-methoxy 1, 4-naphthoquinone. Interestingly, apart from acting as inhibitor, these compounds also act as subversive substrates and subvert the physiological function of enzyme by converting it from an antioxidant to a prooxidant. Both naphthoquinones show a significant effect on redox homeostasis and results in increased reactive oxygen species, resulting in morphological changes and parasite death.

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AIMS: To assess the reliability of ultrasound imaging coupled with Color Power Doppler for monitoring the healing after nonsurgical endodontic therapy. MATERIALS AND METHODS: Ten asymptomatic maxillary anterior teeth with approximately similar-sized periapical radiolucent lesions of average dimension 1.3 - 1.9 cm, as observed on an intraoral periapical radiograph, and confirmed by ultrasound was selected for the study. After confirming the diagnosis all the teeth were subjected to nonsurgical endodontic treatment. Postoperative healing was monitored using postoperative subjective feedback, a radiograph, and an ultrasound with a color power doppler, at intervals of six weeks, three months, and six months. RESULTS: Eight among the ten cases studied showed signs of healing, with an ultrasound, as early as six weeks postoperatively, but the radiographs showed a noticeable change only at the end of three months. At the end of the follow-up period of three months and six months, the findings in terms of change in the lesion size were the same with both the radiograph and ultrasound. Ultrasonography was able to predict the healing very consistently at all recall periods from six weeks onward providing vital information such as changes in vascularity and bone formation as compared to radiographs. CONCLUSIONS: Ultrasound with Color Power Doppler is an efficient tool for monitoring bone healing as compared to the conventionally employed radiographic method.

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Trypanothione reductase (TryR) is a validated drug target against Leishmaniasis. Using integrated computational and experimental approaches, the authors report doxorubicin and mitomycin C, known antitumor agents, as novel inhibitors of TryR of leishmania parasite. Interestingly, these compounds also act as subversive substrates and subvert the physiological function of enzyme by converting it from an anti-oxidant to a pro-oxidant. Possible mechanism of subversive substrate is discussed. Both doxorubicin and mitomycin C show significant effect on redox homeostasis of the parasite and high-leishmanicidal activity. The toxicity studies as well as available toxicity data in literature indicate these compounds to have acceptable toxicity in limited dose.

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Out of various tropical diseases caused by trypanosomatids, leishmaniasis is a life-threatening disease caused by the leishmania parasite. We are targeting the thiol metabolic pathway of the parasite for drug development, and trypanothione reductase (TryR) is a key enzyme of this pathway. It is important to gather significant knowledge about biophysical and intrinsic properties of this enzyme which will be helpful in better understanding of this drug-target enzyme. We report here the modulation of activity and stability of TryR from Leishmania infantum in the presence of various denaturants and pHs. The enzyme is quite stable under high concentration of denaturants and showed better stability compared to TryR of Leishmania donovani, whose sequence differs at only on position (Ala363→Gly). Structural basis of the destabilizing effects is discussed.

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ETHNOPHARMACOLOGICAL RELEVANCE: Nyctanthes arbortristis L. (Oleaceae) is widely used in the traditional medicine of India. The plant is shown to have antibacterial and antileishmanial activities. AIM OF THE STUDY: Evaluation of iridoid glucosides from the plant as inhibitor of trypanothione reductase (TryR), a validated drug target enzyme of the Leishmania parasite. The study contributes towards understanding mechanism of antileishmanial effect of the plant. MATERIALS AND METHODS: TryR of Leishmania parasite is expressed and purified. Iridoid glucosides are isolated from the plant and tested as inhibitor of TryR enzyme of the parasite. RESULTS: Inhibitory constant (K(i)) of various iridoid glucosides ranges from 3.24±0.05 µM to 6.49±0.05 µM. Thus, the molecular mechanism underlying antileishmanial activity of these compounds is mediated through inhibition of TryR. CONCLUSION: The current study also points out towards potential application of iridoid glucosides as novel drugs against the disease.

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Visceral leishmaniasis, most lethal form of Leishmaniasis, is caused by Leishmania infantum in the Old world. Current therapeutics for the disease is associated with a risk of high toxicity and development of drug resistant strains. Thiol-redox metabolism involving trypanothione and trypanothione reductase, key for survival of Leishmania, is a validated target for rational drug design. Recently published structure of trypanothione reductase (TryR) from L. infantum, in oxidized and reduced form along with Sb(III), provides vital clues on active site of the enzyme. In continuation with our attempts to identify potent inhibitors of TryR, we have modeled binding modes of selected tricyclic compounds and quinone derivatives, using AutoDock4. Here, we report a unique binding mode for quinone derivatives and 9-aminoacridine derivatives, at the FAD binding domain. A conserved hydrogen bonding pattern was observed in all these compounds with residues Thr335, Lys60, His461. With the fact that these residues aid in the orientation of FAD towards the active site forming the core of the FAD binding domain, designing selective and potent compounds that could replace FAD in vivo during the synthesis of Trypanothione reductase can be deployed as an effective strategy in designing new drugs towards Leishmaniasis. We also report the binding of Phenothiazine and 9-aminoacridine derivatives at the Z site of the protein. The biological significance and possible mode of inhibition by quinone derivatives, which binds to FAD binding domain, along with other compounds are discussed.

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Leishmaniasis has been ignored for many years mainly because it plagues remote and poor areas. However, recently, it has drawn attention of several investigators, and active research is going on for antileishmanial drug discovery. The current available drugs have high failure rates and significant side effects. Recently, liposomal preparations of amphotericin B are available and have proved to be a better drug, but they are very expensive. Miltefosine is one of the few orally administered drugs that are effective against Leishmania. However, it has exhibited teratogenicity, hence, should not be administered to pregnant women. Thus, the search for novel and improved antileishmanial drugs continue. A rational approach to design and develop new antileishmanials can be to identify several metabolic and biochemical differences between host and parasite that can be exploited as drug target. Moreover, many natural products also have significant antileishmanial activity and are yet to be exploited. In the current review, we aim to bring together various drug targets of Leishmania, recent development in the field, future prospects, and hope in the area.

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AIM: The aim of the present study was to evaluate the effect of occlusal splint therapy by determining the cross-sectional dimension of masseter muscle using ultrasound in patients with temporomandibular joint disc displacement with reduction. METHODS: Twenty-seven patients aged between 20 and 40 years were included in the study. A detailed history was obtained, and a comprehensive clinical examination was carried out. Subjective assessment with structured pro forma was performed pre-occlusal and post-occlusal splint therapy. The objective measurement of the bilateral masseter muscle thickness was recorded using real-time ultrasonography before and after splint therapy. RESULTS: The mean ultrasound thickness of the masseter muscle in the pre-clenching state before splint therapy was 9.45 mm (SD 1.39), and the post-clenching state was 13.15 mm (SD 2.23). After splint therapy, the mean thickness in the pre-clenching state was 9.14 mm (SD 1.31), and the post-clenching state was 12.78 mm (SD 2.23; P<0.001). CONCLUSION: Ultrasonographic measurements of the masseter muscle in patients with temporomandibular joint disc displacement with reduction can be a useful tool to assess the effectiveness of occlusal splint therapy. Such conservative measures can significantly reduce masticatory muscle tenderness, especially of the temporalis and masseter.

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Predicting information regarding the structure of the protein from its sequence still remains an uphill task. Though both are intimately linked, it has been found difficult so far to get a direct correlation between the two. In our present approach we use a simple method based on multiple alignment and phylogeny to derive a correlation between the protein structure and sequence via motif search. The protein families which we have considered are SH2 like, Homeodomain, Leucine rich repeat, Alphabeta knot trefoilknot and ferritin like helix bundle. We have been able to successfully predict the protein families with an average prediction of accuracy of 81%, the highest being 89% and the lowest being 73% on our test data set.

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BACKGROUND: Image-guided fine needle aspiration (FNA) biopsy of deep-seated lesions (e.g., retroperitoneal) has aided preoperative diagnosis and treatment planning. Fine needle aspiration biopsy of pheochromocytomas traditionally has been contraindicated by many authors because of possible hypertensive crisis and fatal hemorrhage. Cytologic features are described for a malignant pheochromocytoma (greater percentage of smaller cells and absence of hyaline globules) with extensive cystic degeneration that was later confirmed by histopathologic, immunohistochemical and ultrastructural studies. CASE: An elderly man was diagnosed with renal cell carcinoma based on clinical examination and ultrasonography. FNA performed on the mass revealed interesting features of pheochromocytoma with an abundance of small cells. CONCLUSION: The cytopathologist should be aware of the cytologic features of pheochromocytoma so as to detect a clinically unsuspected lesion. An increased percentage of smaller cells may be indicative of aggressive tumors.

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