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O D'Cruz

Publications and source records attributed to O D'Cruz.

11 recordsLinked to original sources
PubMed2004

Rational drug design of multifunctional phosphoramidate substituted nucleoside analogs.

This review focuses on our approach to the study of the effect of a series of phosphoramidate substituted nucleoside analogs on model systems for cancer, HIV and fertility. This approach allowed the development of compound WHI-07, an arylphosphoramidate derivative of zidavudine. This compound is a multifunctional agent showing potent activity in the above mentioned model systems. Our rational drug design provided such a powerful derivative with all the necessary characteristic of a drug candidate. Importantly, we have experimental evidence that each of the groups associated with the molecular frame of WHI-07 imparts the multifunctional ability for this agent. In addition, we have also suggested a possible biological pathway for WHI-07 including various products with their therapeutic targets that are formed during the course of its metabolism inside the cell. We also propose which individual moieties in the structure of WHI-07 are responsible for the biological activity from the formation of these metabolites. A detailed structure-activity relationship is presented in the review in connection with various structural modifications of the agent. Application of this active agent in animal models shows the potential usefulness of this agent as a drug candidate. We further plan to utilize gene-chip technology to identify new targets and modes of action using microarrays to measure expression changes in thousands of gene products. In conclusion, we have demonstrated the power of multifunctional drug design to discover drugs to combat various diseases. We believe this is the future direction of the drug discovery process.

Amides↗
PubMed2001

Anticonvulsants-induced chorea: a role for pharmacodynamic drug interaction?

Chorea is a rare side effect of anticonvulsants. We describe three patients who developed chorea secondary to anticonvulsant combination use. A mechanism to explain this finding is proposed. After identification of an index case with anticonvulsant-induced chorea, we reviewed the electronic data base records for all patients with seizures followed in the epilepsy clinics at our university-based hospital for cases of dyskinesia associated with anticonvulsants. Two additional patients, one adult and one pediatric patient were identified. Three patients developed chorea while receiving combination anticonvulsants. Two patients had transient chorea that resolved with withdrawal of one of the drugs. All three patients were using phenytoin and lamotrigine in combination when the chorea started, chorea improved with tapering one of the medications. Polytherapy with certain anticonvulsants may predispose patients to drug-induced chorea. A particular increased risk was seen with combinations that have phenytoin and lamotrigine. This could be due to an additive or a synergistic effect on central dopaminergic pathways.

Anticonvulsants↗
PubMed1996

Mobius syndrome: electrophysiologic studies in seven cases.

Mobius syndrome is characterized by congenital facial diplegia, frequent impairment of gaze, variable involvement of other cranial muscles, and various musculoskeletal anomalies. The site of dysfunction remains debatable. We performed detailed electrophysiologic studies in 5 children and 2 adults with Mobius syndrome to better delineate the pathophysiology of this disorder. Sensory and motor conduction studies were normal in the extremities. Facial compound muscle action potential amplitudes were reduced in all patients. The blink reflex R1 responses were unobtainable unilaterally in 2 patients and unobtainable bilaterally in 3 patients. Otherwise, R1 and R2 latencies were variably prolonged. The jaw jerk and masseter silent periods, tested in 2 patients, were normal. Detailed electromyographic studies of facial muscles revealed multifocal, chronic neurogenic changes. The findings indicate a brain stem process predominantly affecting the facial nuclei and their internuclear connections rather than a supranuclear or muscular site of involvement.

Action Potentials↗
PubMed1988

The effect of fixatives and/or air-drying on the plasma and acrosomal membranes of human sperm.

It has been hypothesized that some fixatives and conditions of slide preparation expose internal sperm antigens and thus are not suitable for demonstrating surface-specific antigens by immunocytochemical assays. This study examined the ability of five fixatives (glutaraldehyde, acetone, methanol, paraformaldehyde, and periodate-lysine-paraformaldehyde [PLP]) and two conditions of slide preparation (air-drying or maintaining sperm in a liquid phase) to maintain the integrity of human spermatozoal membranes at the ultrastructural level as monitored by transmission electron microscopy. Regardless of the fixative employed, air-drying was detrimental to plasma and acrosomal membrane integrity. Acetone and methanol completely disrupted the plasma and acrosomal membranes over the entire sperm surface whether air-drying or liquid phase conditions were employed. Fixation with glutaraldehyde and paraformaldehyde (to a lesser degree) maintained the morphologic integrity of acrosomal and plasma membranes provided the sperm were maintained in a liquid phase. However, glutaraldehyde and paraformaldehyde fixation increased the postfixation binding of immunoglobulins to the sperm surface. We concluded that immunocytochemistry at the light microscopy level may imply erroneous interpretations regarding antigen/antibody interactions on the sperm plasma membrane surface unless care is taken to verify that the antibodies of interest are binding to the antigenically intact plasma or acrosomal membrane.

Acetone↗
PubMedDate not supplied

Möbius syndrome in infant exposed to cocaine in utero.

The pathophysiology of Möbius syndrome has been debated for decades. A vascular etiology is currently favored because it explains the wide clinical spectrum of this syndrome. An infant is reported who was born with Möbius syndrome after a pregnancy complicated by heavy maternal use of cocaine and alcohol. We speculate that cocaine-induced vasoconstriction at a critical time of cerebrovascular development produced a vascular disruption sequence leading to the Möbius syndrome.

Adult↗