Biomedical subjects

H N Lin

Publications and source records attributed to H N Lin.

At least 37 records · Page 2Linked to original sources

PubMed1996

Plasma haloperidol and reduced haloperidol concentrations in a geriatric population.

Haloperidol (HL) and reduced haloperidol (RH) plasma concentrations were measured in geriatric patients (n = 45) and schizophrenic patients (n = 8). In the elderly patients, HL doses were 1-4 mg/day while only 2 mg/day was used in the schizophrenics. At HL 2 mg/day dose in both age groups, mean plasma HL levels were approximately twice as high in the elderly patients compared to the schizophrenics (1.39 +/- 0.82 vs. 0.56 +/- 0.23 ng/ml, p < 0.02). RH plasma concentrations were almost 5 times greater in the elderly patients (0.54 +/- 0.35 vs. 0.09 +/- 0.05 ng/ml, p < 0.0001). These results suggest that HL plasma concentrations in the elderly are greater than in adult schizophrenic patients treated with similar HL doses.

Adult↗

PubMed1996

A practical loading dose method for converting schizophrenic patients from oral to depot haloperidol therapy.

BACKGROUND: Haloperidol decanoate is a long-acting depot antipsychotic agent used for the treatment of schizophrenic patients. The decanoate formulation was developed to treat schizophrenics who have a history of noncompliance with oral medication. Studies of techniques to convert from oral to depot therapy have not utilized the pharmacokinetics of the decanoate formulation. This study is a prospective evaluation for converting patients from oral to depot treatment. METHOD: Twenty-one patients meeting DSM-III-R criteria for schizophrenia participated in the study. Patients were treated with oral haloperidol for 6 weeks and then were switched to decanoate. Haloperidol decanoate 100 mg was administered on a weekly basis for the first 4 weeks. Afterward, injection intervals were increased to every 2 weeks and then to every 4 weeks. Plasma haloperidol concentrations were obtained prior to the next injection and assayed by HPLC with electrochemical detection. Patients were monitored by the psychiatrists and nursing staff for symptoms of clinical deterioration. RESULTS: All patients completed the conversion trial during the first 4 weeks without any problems or adverse side effects. By the third week, mean plasma haloperidol concentrations from the decanoate injections were comparable with those of the 10-mg oral haloperidol treatment (7.95 +/- 4.94 ng/mL vs. 7.79 +/- 4.79 ng/mL). Steady-state conditions for the decanoate therapy were achieved by the fourth week. CONCLUSION: These findings suggest that schizophrenic patients can be easily converted from oral to depot therapy without problems. Further studies with haloperidol decanoate and its conversion from oral treatment utilizing plasma concentrations are needed.

Administration, Oral↗

PubMed1995

Phosphatidylcholines with sn-1 saturated and sn-2 cis-monounsaturated acyl chains. Their melting behavior and structures.

Recently, we have shown by high resolution differential scanning calorimetry that the position of a cis double bond (delta-bond) in a series of 1-stearoyl-2-octadecenoyl- phosphatidylcholines can affect the phase transition temperature (Tm) or enthalpy (delta H) of the gel-to-liquid crystalline phase transition of this series of lipids in the following manner. The value of Tm (or delta H) is minimal when the delta-bond is positioned at C(11) in the sn-2 acyl chain; in addition, this value increases steadily as the delta-bond migrates toward either end of the acyl chain, resulting in a symmetrical, inverted bell-shaped profile (Wang, Z.-q., Lin, H.-n., Li, S., and Huang, C. (1995) J. Biol. Chem. 270, 2014-2023). In this communication, we have further demonstrated the inverted bell-shaped profile of Tm using 1-arachidoyl-2-eicosenoyl-phosphatidylcholines. In addition, we have extended the lipid series of 1-stearoyl-2-octadecenoyl-phosphatidylcholines to include 1-arachidoyl-2-octadecenoyl- phosphatidylcholines and 1-behenoyl-2-octadecenoyl-phosphatidylcholine, each series with a delta-bond at varying carbon position of 6, 7, 9, 11, 12, and 13. Calorimetric results obtained with these three series of lipids indicate that the inverted bell-shaped curve shifts toward higher temperatures in a nonuniform manner as the saturated sn-1 acyl chain length increases from 17 to 19 and then to 21 C-C bond lengths. Specifically, the Tm (or delta H) values are nearly identical for these cis-monoenoic lipids when their delta-bonds are positioned at C(13). Based on the height of the rotational energy barrier obtained with molecular mechanics calculations, it is evident that the rotational flexibility of the single C-C bond adjacent to the delta-bond in 1-stearoyl-2-octadecenoyl-phosphatidylcholine increases as the delta-bond migrates from C(9) to C(13). The differential scanning calorimetry results obtained with the three series of lipids can thus be attributed to an increase in the rotational flexibility of the short chain segment succeeding the C(14) atom in the sn-2 octadecenoyl chain. In this communication, we also propose that in the gel-state bilayer of sn-1 saturated/sn-2 cis-monounsaturated phosphatidylcholine the entire length of the shorter segment of the sn-2 acyl chain acts as a structural perturbing element; hence, it is mainly responsible for the large lower Tm of the monoenoic lipid relative to the saturated counterpart. Finally, two general equations relating Tm with the structural parameters of cis-monoenoic phosphatidylcholines are presented.(ABSTRACT TRUNCATED AT 400 WORDS)

Calorimetry, Differential Scanning↗

PubMed1995

A calorimetric study of binary mixtures of 1-octadecanoyl-2-decanoyl-sn-glycero-3-phosphoethanolamine and dimyristoyl phosphatidylethanolamine.

Model membranes composed of 1-octadecanoyl-2-decanoyl-sn-glycero-3- phosphoethanolamine and dimyristoyl phosphatidylethanolamine have been studied calorimetrically. 1-Octadecanoyl-2-decanoyl-sn-glycero-3- phosphoethanolamine is a highly asymmetric mixed-chain lipid, whereas dimyristoyl phosphatidylethanolamine is an identical-chain lipid with the same molecular weight. Calorimetric results indicate that these two lipids with a common molecular weight are completely miscible in the two-dimensional plane of the lipid bilayer in the liquid-crystalline state and that they are only partially miscible in the gel-state bilayer. Specifically, binary mixtures of these two lipids form eutectic phase diagrams at pH 7.4 and 10.0.

Calorimetry, Differential Scanning↗

PubMed1995

Phase transition behavior and molecular structures of monounsaturated phosphatidylcholines. Calorimetric studies and molecular mechanics simulations.

High resolution differential scanning calorimetric studies were performed to investigate the thermotropic phase behavior of 26 molecular species of sn-1 saturated/sn-2 monounsaturated phosphatidylcholines. In parallel with calorimetric studies, the energy-minimized structures and steric energies of the diglyceride moieties of these monoenoic lipids were determined using a molecular mechanics approach. The combined calorimetric and computational studies led to the following results and conclusions. (i) When a single cis-carbon-carbon double bond (delta) is incorporated into a saturated diacylphosphatidylcholine molecule at any position within the central segment of the long sn-2 acyl chain, the resulting monoenoic lipid molecules will, in excess water, exhibit reduced phase transition temperature (Tm) and transition enthalpy (delta H) as they undergo the gel to liquid-crystalline phase transition. The Tm and delta H-lowering effects of the delta bond can be attributed to a decrease in the chain length of the sn-2 acyl chain, a change in the chain length difference between the sn-1 and sn-2 acyl chains, and a local perturbation of the chain-chain van der Waals interaction in the vicinity of the delta bond. (ii) For a series of positional isomers of 1-stearoyl-2-cis-octadecenoylphosphatidylcholine, C(18):C(18:1 delta n)PC, with a delta bond at different positions along the sn-2 acyl chain, the Tm value depends critically on the position of the delta bond. Specifically, the Tm value is minimal as the delta bond is located at the geometric center of the linear segment of the sn-2 acyl chain, and the Tm value is progressively increased as the delta bond migrates toward either end of the sn-2 acyl chain. (iii) The various monoenoic phosphatidylcholines under study can be divided into two groups. The Tm values of most lipids in each group can be correlated in an identical manner with their structural parameters, yielding a common Tm-structure relationship.

Calorimetry, Differential Scanning↗

PubMed1995

Haloperidol plasma concentrations in Taiwanese psychiatric patients.

Haloperidol and reduced haloperidol are interconverted. The plasma concentrations of these two butyrophenones have been suggested to be important factors in determining the clinical effect of haloperidol treatment. The steady-state plasma concentrations of haloperidol and reduced haloperidol were measured in 322 Taiwanese schizophrenic patients using high performance liquid chromatography. The daily doses of haloperidol varied from 5 to 200 mg (mean +/- SD, 35.3 +/- 34.6 mg). There was a positive correlation between plasma concentrations and doses, following the equation: haloperidol concentration (ng/mL) = 0.88 x dose (mg/day)-1.66. However, the interpatient variation in haloperidol concentrations was up to ten-fold even in patients receiving the same dose (20 mg/day, n = 88). The expected values were about 10% to 50% higher than those reported in Caucasian patients. The plasma reduced haloperidol concentrations were significantly lower than, and correlated with, those of haloperidol in patients with haloperidol levels lower than 25 ng/mL. However, once haloperidol exceeded 25 ng/mL, reduced haloperidol levels rapidly elevated and appeared significantly higher than haloperidol levels. While haloperidol could reach its steady state in about 1 week, reduced haloperidol needed at least 4 weeks to do so. Haloperidol doses of less than 30 mg/day and plasma concentrations lower than 25 ng/mL are recommended for most Chinese patients.

Adult↗

PubMed1994

Calorimetric studies and molecular mechanics simulations of monounsaturated phosphatidylethanolamine bilayers.

This investigation was designed to determine how information about the lipid chain melting and structural characteristics of sn-1 saturated/sn-2 monounsaturated phosphatidylethanolamines, a subclass of naturally occurring phospholipids, can be generalized among these lipid molecules. Specifically, 30 molecular species of sn-1 saturated/sn-2 unsaturated monoenoic phosphatidylethanolamines were semi-synthesized. The phase transition behavior of these monoenoic lipids in excess water was studied calorimetrically. The computer-based molecular mechanics approach was used to simulate the energy-minimized structures and to calculate steric energies for the diglyceride moieties of some of the 30 monoenoic lipid molecules, at T < Tm, in various aggregated states. These combined calorimetric and computational studies led to the following results and conclusions. 1) For a homologous series of monoenoic lipids with a common molecular weight and with a cis-double bond at various positions along the sn-2 acyl chain, the characteristic reduction of the main phase transition temperature (Tm) is proposed to be a result of an entropy-driven phenomenon. 2) The maximal decrease in the Tm for bilayers prepared from four series of monoenoic phosphatidylethanolamines containing a sn-2 octadecenoyl chain is shown by interpolation of calorimetric data to occur uniquely when the cis double bond is located commonly between C(10) and C(11) positions from the carboxyl end. 3) Monoenoic phosphatidylethanolamines can be divided into two groups. The Tm values obtained with bilayers of monoenoic lipids within each group can be systematically correlated with their structural parameters, leading to the derivation of two general Tm-structure relationships.

Calorimetry, Differential Scanning↗

PubMed1994

On the main phase transition temperatures of highly asymmetric mixed-chain phosphatidylcholines.

The highly asymmetric mixed-chain phosphatidylcholines or C(X):C(Y)PC, which can self-assemble at T < Tm into the mixed interdigitated gel-state bilayer in excess water, can be divided into two groups. Group I consists of C(X):C(Y)PC with X > Y, and Group II consists of C(X):C(Y)PC with X < Y. The main phase transition temperatures (Tm) of these C(X):C(Y)PC have been analyzed in terms of two structural parameters (delta and Nf). Specifically, these structural parameters are related to the packing geometry of the lipid's acyl chains as the lipid molecules are packed either in a mixed (delta) or a hypothetically partially (Nf) interdigitated packing motif at T < Tm. Based on 28 and 29 Tm values of Group I and II C(X):C(Y)PC, two general equations are derived, respectively, by multiple regression analyses. These equations correlate systematically the Tm values of Group I and II phosphatidylcholines with their corresponding structural parameters. Using these two derived equations, the Tm values of a total of 92 molecular species of C(X):C(Y)PC are generated, and these calculated Tm values can be considered as the reliably predicted Tm values for highly asymmetric C(X):C(Y)PC which have delta C/CL values within the range of 0.42-0.66.

Calorimetry, Differential Scanning↗

PubMed1994

Interconversion of bilayer phase transition temperatures between phosphatidylethanolamines and phosphatidylcholines.

High-resolution differential scanning calorimetric studies were performed to investigate the thermotropic phase behavior of 31 molecular species of phosphatidylethanolamines in excess water. Upon reheating, the aqueous dispersions of these lipids undergo the gel to liquid-crystalline phase transitions at well defined temperatures (Tm). These Tm values were shown to relate to the structural parameters of the underlying lipid molecules in a characteristic manner. Based on these observations, an interconversion of the Tm values between saturated phosphatidylethanolamines and phosphatidylcholines is established quantitatively for the first time.

Calorimetry, Differential Scanning↗

PubMed1994

Identification and characterization of kink motifs in 1-palmitoyl-2-oleoyl- phosphatidylcholines: a molecular mechanics study.

As a cis carbon-carbon double bond (delta) is introduced into the middle of an isolated all-trans hydrocarbon chain, it can be shown by molecular graphics that this delta-bond makes a bend of 130 degrees in the chain axis, thus producing a boomerang-like conformation. Such a bent structure, indeed, has been detected experimentally for oleic acid by x-ray crystallography (Abrahamson and Ryderstedt-Nahringbaur, 1962). Membrane diacyl phospholipids are largely mixed-chain lipids containing a saturated sn-1 acyl chain and an unsaturated sn-2 acyl chain. 1-Palmitoyl-2-oleoyl-phosphatidylcholine (POPC), the most abundant phospholipid in animal cell membranes, is a typical example in which the sn-2 acyl chain is the acyl chain of an oleic acid. However, this sn-2 acyl chain of POPC is unlikely to adopt a boomerang-like configuration in the gel-state lipid bilayer due to the steric hindrance imposed by neighboring chains. Instead, it has been suggested that the oleate chain in POPC is kinked in the shape of a crankshaft in the gel-state bilayer (Huang, 1977; Lagaly et al., 1977), because POPC with such a kinked sn-2 acyl chain, which is denoted here as the secondary structural element or motif, can pack efficiently against other neighboring phospholipids. In this communication, 16 different types of secondary structural elements or motifs are derived for POPC at T < Tm based on a single protocol guided by two-dimensional steric contour maps and computer-based molecular graphics. After subjecting these derived molecular species to energy minimization using the molecular mechanics method, the number of the secondary structural motifs is reduced to 13 as a result of conformational degeneracy. The structure and steric energy of each of the energy-minimized lipid rotomers are presented in this communication. Furthermore, these rotomers packed in small clusters are also simulated to mimic the lipid bilayer structure of 1-palmitoyl-2-oleoyl-phosphatidylcholines at T < Tm.

Calorimetry↗

PubMed1993

Calorimetric studies of fully hydrated phosphatidylcholines with highly asymmetric acyl chains.

We have semi-synthesized 52 molecular species of saturated diacyl mixed-chain phosphatidylcholines. All 52 phosphatidylcholine molecules are highly asymmetrical with delta C/CL values in the range of 0.43-0.63. The aqueous dispersions of these phosphatidylcholines have been studied by the high-resolution differential scanning calorimetric (DSC) technique. Upon heating, the lipid dispersions prepared individually from these 52 phosphatidylcholines all exhibit a sharp, single, endothermic peak at a characteristic temperature or Tm, implying that the self-assembled lipid molecules in excess water undergo the mixed interdigitated gel to the liquid-crystalline phase transition. The Tm values obtained from aqueous lipid dispersions prepared from these mixed-chain phospholipids have been analyzed based on the molecular packing model of the mixed interdigitated bilayer, and a linear relationship between the Tm and (delta C)-1 for various phospholipids at a constant value of delta is observed. Based on these linear relationships, empirical equations are derived to predict the Tm values for highly asymmetrical mixed-chain phosphatidylcholines with delta C/CL values in the range of 0.43-0.63. The predictive power of these empirical equations is shown to be very good, since a comparison between the predicted and the experimental data indicates that the largest relative error in Kelvin is only 0.4%. A table containing 81 predicted Tm values for highly asymmetrical mixed-chain phosphatidylcholines is presented. The definitions of the various structural parameters such as delta C, CL, delta C/CL and delta are given in the text.

Calorimetry, Differential Scanning↗

PubMed1993

Dependence of the bilayer phase transition temperatures on the structural parameters of phosphatidylcholines.

Most saturated diacyl phosphatidylcholines C(X):C(Y)PC (saturated 1,2-diacyl-sn-glycero-3-phosphocholine with X carbons in the sn-1 acyl chain and Y carbons in the sn-2 acyl chain), in excess water, can self-assemble into lamellae which, upon heating, may undergo multiple thermotropic phase transitions at well-defined, discrete temperatures. The transition temperature corresponding to the main or the gel to liquid-crystalline phase transition (Tm) is known for many bilayers of fully hydrated phosphatidylcholines. In this study, we have analyzed the Tm values of 44 molecular species of phosphatidylcholines in terms of their structural and packing characteristics in the gel-state bilayer. Two general equations are thus derived: Tm = 162.26-3651.71 (1/N) - 88.42 (delta C/N) for C(X):C(Y)PC with X > or = Y, and Tm = 157.68-3525.44 (1/N) - 93.28 (delta C/N) for C(X):C(Y)PC with X < Y. Here, N is the minimal hydrophobic thickness of the dimeric C(X):C(Y)PC in the gel-state bilayer and delta C is the effective chain length difference between the sn-1 and sn-2 acyl chains for the monomeric C(X):C(Y)PC in the gel-state bilayer. The advantage of these two equations in predicting the Tm values for phosphatidylcholines with delta C/CL values in the range of 0.07 to 0.40 is their simplicity. A figure containing a total of 173 calculated Tm values is also presented.

Computer Simulation↗

PubMed1993

Plasma homovanillic acid and treatment response in a large group of schizophrenic patients.

Plasma levels of homovanillic acid (pHVA), a metabolite of dopamine, were measured in ninety-five Chinese schizophrenic patients free of neuroleptics for at least four weeks. These patients were treated with classical antipsychotics for six weeks. Pretreatment pHVA was positively correlated with the subsequent clinical response (r = 0.408, p < 0.0001). Good responders (BPRS improvement > or = 50%, n = 47) had higher pretreatment pHVA levels than poor responders (BPRS improvement < 50%, n = 48) (15.7 +/- 8.4 ng/ml versus 9.9 +/- 3.7 ng/ml, p < 0.0001). A higher than 15 ng/ml pretreatment pHVA level was associated with a more consistent clinical response to the subsequent treatment. Using a pHVA level of 12 ng/ml as a demarcation point, 72% of patients (34 of 47) who had pHVA > or = 12 responded whereas 65% (31 of 48) who had < 12 did not respond (chi-square = 13.02, p < 0.0001). These results suggest that higher pretreatment pHVA levels may predict a better clinical response to antipsychotics. Based upon the pHVA findings, two hypothetical subtypes of schizophrenia are proposed.

Adolescent↗

PubMed1993

Energy-minimized structures and packing states of a homologous series of mixed-chain phosphatidylcholines: a molecular mechanics study on the diglyceride moieties.

Phosphatidylcholines or C(X):C(Y)PC, quantitatively the most abundant lipids in animal cell membranes, are structurally composed of two parts: a headgroup and a diglyceride. The diglyceride moiety consists of the glycerol backbone and two acyl chains. It is the wide diversity of the acyl chains, or the large variations in X and Y in C(X):C(Y)PC, that makes the family of phosphatidylcholines an extremely complex mixture of different molecular species. Since most of the physical properties of phospholipids with the same headgroup depend strongly on the structures of the lipid acyl chains, the energy-minimized structure and steric energy of each diglyceride moiety of a series of 14 molecular species of phosphatidylcholines with molecular weights identical to that of dimyristoylphosphatidylcholine without the headgroup are determined in this communication by molecular mechanics (MM) calculations. Results of two types of trans-bilayer dimer for each of the 14 molecular species of phosphatidylcholines are also presented; specifically, the dimeric structures are constructed initially based on the partially interdigitated and mixed interdigitated packing motifs followed subsequently by the energy-minimized refinement with MM calculations. Finally, tetramers with various structures to model the lateral lipid-lipid interactions in a lipid bilayer are considered. Results of laborious MM calculations show that saturated diacyl C(X):C(Y)PC with delta C/CL values greater than 0.41 prefer topologically to assemble into tetramers of the mixed interdigitated motif, and those with delta C/CL values less than 0.41 prefer to assemble into tetramers with a repertoire of the partially interdigitated motif. Here, delta C/CL, a lipid asymmetry parameter, is defined as the normalized acyl chain length difference between the sn-1 and sn-2 acyl chains for a C(X):C(Y)PC molecule; an increase in delta C/CL value is an indication of increasing asymmetry between the two lipid acyl chains. These computational results are in complete accord with the calorimetric data presented previously from this laboratory (H-n. Lin, Z-q. Wang, and C. Huang. 1991. Biochim. Biophys. Acta. 1067:17-28).

Animals↗

PubMed1992

Comparison of haloperidol and reduced haloperidol plasma levels in four different ethnic populations.

1. Plasma haloperidol and reduced haloperidol concentration were measured in four ethnic populations. 2. Plasma samples were obtained under steady-state conditions and obtained 10-12 hours post bedtime dose and prior to the morning dose. 3. Haloperidol and reduced haloperidol plasma levels were assayed by radioimmunoassay and liquid chromatography. 4. A wide interpatient variability between haloperidol dose and plasma concentration was observed for each ethnic group. 5. The Chinese group differed from the other ethnic populations. 6. A nonlinear relationship was observed between haloperidol and reduced haloperidol plasma levels in each ethnic group. Further, the relationship of haloperidol to reduced haloperidol plasma levels differed for each ethnic group. These results suggest that various ethnic groups could metabolize haloperidol and reduced haloperidol differently.

Black or African American↗

PubMed1991

The influence of acyl chain-length asymmetry on the phase transition parameters of phosphatidylcholine dispersions.

The influence of acyl chain-length asymmetry on the thermodynamic parameters (Tm, delta H, and delta S) associated with the reversible main phase transition of aqueous dispersions prepared from saturated diacyl phosphatidylcholines was studied by high-resolution differential scanning calorimetry. Two series of saturated diacyl phosphatidylcholines, grouped according to their molecular weights of 678 and 706, with a total number of 25 molecular species were examined. The normalized acyl chain-length difference between the sn-1 and sn-2 acyl chains for a given phospholipid molecule in the gel-state bilayer is expressed quantitatively by the structural parameter delta C/CL, and the values of delta C/CL for the two series of lipids under study vary considerably from 0.04 to 0.67. When the value of delta C/CL is within the range of 0.09-0.40, it was shown that the thermodynamic parameters are, to a first approximation, a linear function of delta C/CL with a negative slope. In addition, the experimental Tm values and the predicted Tm values put forward by Huang (Biochemistry (1991) 30, 26-30) are in very good agreement. Beyond the point of delta C/CL = 0.41, the influence of acyl chain-length asymmetry on the thermodynamic parameters deviates significantly from a linear function. In fact, within the range of delta C/CL values of 0.42-0.67, the thermodynamic parameters in the Tm (or delta H) vs. delta C/CL plot were shown to be bell-shaped with the maximal Tm (or delta H) at delta C/CL = 0.57. These results are discussed in terms of changes in the acyl chain packing modes of various phosphatidylcholine molecules within the gel-state bilayer in excess water.

Calorimetry, Differential Scanning↗

PubMed1991

Thermotropic and mixing behavior of mixed-chain phosphatidylcholines with molecular weights identical with that of L-alpha-dipalmitoylphosphatidylcholine.

The thermotropic phase behavior of 10 mixed-chain phosphatidylcholines, in excess water, has been examined and compared with that of identical-chain C(16):C(16)PC by using high-resolution differential scanning calorimetry (DSC). The molecular weights (MW) of these 11 molecular species are the same, but their delta C/CL values, or the normalized chain length differences, vary considerably, ranging from 0.035 to 0.540. The thermodynamic parameters (Tm, delta H, and delta S) associated with the main phase transitions for these lipid dispersions exhibit biphasic V-shaped curves, when plotted against delta C/CL. Similar characteristic curves have been reported previously for aqueous dispersions of mixed-chain phosphatidylcholines with MW identical with that of C(17):C(17)PC [Lin et al. (1990) Biochemistry 29, 7063-7072]. The initial decrease in Tm (delta H or delta S) with increasing values of delta C/CL is attributed to the progressive increase in the magnitude of the chain-terminal perturbations on the conformational statistics of the adjacent hydrocarbon chains and hence the lateral chain-chain interactions of these mixed-chain phosphatidylcholines in the gel-state bilayer. At delta C/CL approximately equal to 0.42, the chain-end perturbation is presumably at its maximum; beyond this point, the highly asymmetric phosphatidylcholines are proposed to pack, at T less than Tm, into the mixed interdigitated bilayer. In this new packing mode, the methyl ends of the longer acyl chains are relocated at the interfaces between the hydrocarbon core of the bilayer and the aqueous medium. This disposition of the bulky chain ends releases a certain degree of chain-chain packing disorders, leading to an increase in Tm (delta H or delta S) with increasing delta C/CL.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1991

Dose-dependent reduced haloperidol/haloperidol ratios in schizophrenic patients.

Plasma haloperidol (HAL) and reduced HAL (RHAL) concentrations were measured in 113 Chinese schizophrenic patients. Daily doses of HAL ranged from 8 to 65 mg. Samples were obtained under steady-state conditions and drawn 10-12 hours after the bedtime dose and before the morning dose. In all, 313 blood samples were collected. Multiple samples were obtained at the same doses in 63 patients and at two or three different doses in 31 patients. HAL and RHAL concentrations were assayed by high performance liquid chromatography. Interpatient variation in plasma HAL levels at a given dosage was up to sixfold. However, there was a high positive correlation between plasma levels and daily dosages with the equation of HAL plasma level (ng/ml) = 0.88 x dosage (mg/day) -0.56 or 46.0 x dosage (mg/day/kg) + 0.28. The expected values are about 15-55% higher than those obtained from non-Chinese patients as reported in the literature. The RHAL/HAL ratios were dose-dependent. The greater the dose used, the higher the ratio. An upper therapeutic limit of plasma HAL level is suggested to be 25 ng/ml, which can be achieved at dosages about 30 mg/day in most Chinese patients. Based upon the dose-dependent increase in RHAL/HAL ratios, the importance of RHAL in determining the therapeutic benefit of HAL treatment is discussed.

Adolescent↗